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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="CEBPA-Associated Familial Acute Myeloid Leukemia (AML)" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2021/02/18" /><meta name="citation_author" content="Kiran Tawana" /><meta name="citation_author" content="Jude Fitzgibbon" /><meta name="citation_pmid" content="20963938" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK47457/" /><meta name="citation_keywords" content="CEBPA-Dependent Familial Acute Myeloid Leukemia" /><meta name="citation_keywords" content="CEBPA-Dependent Familial Acute Myeloid Leukemia" /><meta name="citation_keywords" content="CCAAT/enhancer-binding protein alpha" /><meta name="citation_keywords" content="CEBPA" /><meta name="citation_keywords" content="CEBPA-Associated Familial Acute Myeloid Leukemia (AML)" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="CEBPA-Associated Familial Acute Myeloid Leukemia (AML)" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Kiran Tawana" /><meta name="DC.Contributor" content="Jude Fitzgibbon" /><meta name="DC.Date" content="2021/02/18" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK47457/" /><meta name="description" content="CEBPA-associated familial acute myeloid leukemia (AML) is defined as the presence of a heterozygous germline CEBPA pathogenic variant in an individual with AML and/or family in which more than one individual has AML. In contrast, sporadic CEBPA-associated AML is defined as AML in which a CEBPA pathogenic variant(s) is identified in leukemic cells but not in the non-leukemic cells. In the majority of individuals, the age of onset of familial AML appears to be earlier than sporadic AML; disease onset has been reported in persons as young as age 1.8 years and up to age 50 years. The prognosis of CEBPA-associated familial AML appears to be favorable compared with sporadic CEBPA-associated AML. Individuals with CEBPA-associated familial AML who have been cured of their initial disease may be at greater risk of developing additional independent leukemic episodes, in addition to the risk of relapse from preexisting clones." /><meta name="og:title" content="CEBPA-Associated Familial Acute Myeloid Leukemia (AML)" /><meta name="og:type" content="book" /><meta name="og:description" content="CEBPA-associated familial acute myeloid leukemia (AML) is defined as the presence of a heterozygous germline CEBPA pathogenic variant in an individual with AML and/or family in which more than one individual has AML. In contrast, sporadic CEBPA-associated AML is defined as AML in which a CEBPA pathogenic variant(s) is identified in leukemic cells but not in the non-leukemic cells. In the majority of individuals, the age of onset of familial AML appears to be earlier than sporadic AML; disease onset has been reported in persons as young as age 1.8 years and up to age 50 years. The prognosis of CEBPA-associated familial AML appears to be favorable compared with sporadic CEBPA-associated AML. Individuals with CEBPA-associated familial AML who have been cured of their initial disease may be at greater risk of developing additional independent leukemic episodes, in addition to the risk of relapse from preexisting clones." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK47457/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/gene/cebpa-aml/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK47457/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script><meta name="book-collection" content="NONE" />
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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK47457_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK47457_dtls__"><div>Adam MP, Feldman J, Mirzaa GM, et al., editors.</div><div>Seattle (WA): <a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>; 1993-2025.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/gene/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search GeneReviews" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search GeneReviews" submit="false" style="padding: 0.1em 0.4em;" /></div></form><div><ul class="inline_list"><li><a href="/books/n/gene/advanced/">GeneReviews Advanced Search</a></li><li style="margin-left:.5em"><a href="/books/n/gene/helpadvsearch/">Help</a></li></ul></div></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/cdkl5-def/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/chchd10-dis/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK47457_"><span class="title" itemprop="name"><i>CEBPA-</i>Associated Familial Acute Myeloid Leukemia (AML)</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: <i>CEBPA</i>-Dependent Familial Acute Myeloid Leukemia</div><p class="contrib-group"><span itemprop="author">Kiran Tawana</span>, MBChB, FRCPath, PhD and <span itemprop="author">Jude Fitzgibbon</span>, BA, PhD.</p><a data-jig="ncbitoggler" href="#__NBK47457_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK47457_ai__"><div class="contrib half_rhythm"><span itemprop="author">Kiran Tawana</span>, MBChB, FRCPath, PhD<div class="affiliation small">Barts Cancer Institute
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Queen Mary University of London
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London, United Kingdom<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ku.shn.sekoorbnedda@anawat.narik" class="oemail">ku.shn.sekoorbnedda@anawat.narik</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Jude Fitzgibbon</span>, BA, PhD<div class="affiliation small">Barts Cancer Institute
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Queen Mary University of London
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London, United Kingdom<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ku.ca.lumq@nobbigztif.j" class="oemail">ku.ca.lumq@nobbigztif.j</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">October 21, 2010</span>; Last Update: <span itemprop="dateModified">February 18, 2021</span>.</p><p><em>Estimated reading time: 22 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="cebpa-aml.Summary" itemprop="description"><h2 id="_cebpa-aml_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>CEBPA-</i>associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> acute myeloid leukemia (AML) is defined as the presence of a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in an individual with AML and/or family in which more than one individual has AML. In contrast, <a class="def" href="/books/n/gene/glossary/def-item/sporadic/">sporadic</a> <i>CEBPA</i>-associated AML is defined as AML in which a <i>CEBPA</i> pathogenic variant(s) is identified in leukemic cells but not in the non-leukemic cells. In the majority of individuals, the age of onset of familial AML appears to be earlier than sporadic AML; disease onset has been reported in persons as young as age 1.8 years and up to age 50 years. The prognosis of <i>CEBPA-</i>associated familial AML appears to be favorable compared with sporadic <i>CEBPA</i>-associated AML. Individuals with <i>CEBPA</i>-associated familial AML who have been cured of their initial disease may be at greater risk of developing additional independent leukemic episodes, in addition to the risk of relapse from preexisting clones.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML is established by identification of a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in a specimen that contains only non-leukemic cells from an individual and/or family with AML.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations</i>: Treatment usually includes cytarabine/anthracycline-based induction and cytarabine-based consolidation chemotherapy. Hematopoietic stem cell transplantation (HSCT) from a volunteer unrelated donor or appropriately screened family member should be reserved for individuals failing to achieve remission following standard induction therapy or for disease recurrence. Whenever possible, persons with AML should be treated as part of a clinical trial protocol.</p><p><i>Surveillance</i>: Similar to that for other forms of AML; because of the increased risk of late leukemia recurrence in persons with <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML, lifelong surveillance is recommended. Asymptomatic individuals should have a CBC every six to 12 months and bone marrow examination for CBC abnormalities.</p><p><i>Agents/circumstances to avoid</i>: Use of sib or related donors for HSCT without prior assessment of the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in the donor.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>Predisposition to <i>CEBPA-</i>associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner. Most individuals diagnosed with <i>CEBPA</i>-associated familial AML have had an affected parent who shares the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. Germline <i>CEBPA</i> pathogenic variants exhibit complete or near-complete <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> for the development of AML in families reported to date. Each child of an affected individual has a 50% chance of inheriting the germline pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the germline <i>CEBPA</i> pathogenic variant in the family is known.</p></div></div><div id="cebpa-aml.Diagnosis"><h2 id="_cebpa-aml_Diagnosis_">Diagnosis</h2><div id="cebpa-aml.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>CEBPA-</i>associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> acute myeloid leukemia (AML) <b>should be suspected</b> in individuals with the following clinical and supportive laboratory findings.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Individuals with AML who also have a family history of AML</div></li><li class="half_rhythm"><div>Individuals who have developed AML at an early age (<50 years)</div></li></ul><p>
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<b>Supportive laboratory findings</b>
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</p><ul><li class="half_rhythm"><div>Typically, individuals with AML presenting before age 50 years with pathogenic variants in both copies of <i>CEBPA</i> (<i>CEBPA</i> double mutation [<i>CEBPA</i>dm]) in tumor DNA</div></li><li class="half_rhythm"><div>In the majority of individuals, a normal <a class="def" href="/books/n/gene/glossary/def-item/karyotype/">karyotype</a> detected in leukemic cells</div></li><li class="half_rhythm"><div>A preponderance of French-American-British Cooperative Group AML Classification subtypes M1 or M2 as established by morphologic analysis of peripheral blood or bone marrow blasts</div></li><li class="half_rhythm"><div>Auer rods seen in blasts (i.e., abnormal, needle-shaped, or round, light blue- or pink-staining inclusions found in the cytoplasm of leukemic cells)</div></li><li class="half_rhythm"><div>Aberrant CD7 expression on blasts as demonstrated by flow cytometry</div></li></ul><p>For this <i>GeneReview</i>, the following definitions apply:</p><ul><li class="half_rhythm"><div><b><i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML</b> is defined by the presence of a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. A germline pathogenic variant may be inherited or <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>.</div></li><li class="half_rhythm"><div><b>Sporadic <i>CEBPA-</i>associated</b>
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<b>AML</b> is defined as AML in which a somatic <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>(s) is acquired in leukemic cells alone; these variants are absent in all of the individual's non-leukemic cells (see <a href="#cebpa-aml.Molecular_Genetics">Molecular Genetics</a>).</div></li></ul></div><div id="cebpa-aml.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> (see <a href="/books/NBK47457/table/cebpa-aml.T.molecular_genetic_testing_us/?report=objectonly" target="object" rid-ob="figobcebpaamlTmoleculargenetictestingus">Table 1</a>). Because <i>CEBPA</i>-associated familial AML develops from cells that have a pathogenic (cancer-predisposing) variant in both copies of <i>CEBPA,</i> leukemic cells frequently demonstrate both a germline and a somatic <i>CEBPA</i> variant. The germline pathogenic variant is typically a <a class="def" href="/books/n/gene/glossary/def-item/frameshift-variant/">frameshift variant</a> located in the <i>CEBPA</i> region encoding the N-terminal C/EBPα protein, while the <a class="def" href="/books/n/gene/glossary/def-item/somatic-pathogenic-variant/">somatic pathogenic variant</a> acquired in leukemic cells is typically in the region encoding the C terminal (see <a href="#cebpa-aml.Molecular_Genetics">Molecular Genetics</a>).</p><p>Note: In the literature, the terms <i>CEBPA</i>dm and <i>CEBPA</i>sm may be used. These terms refer to leukemic cells with <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>CEBPA</i> pathogenic variants ("<i>d</i>ouble <i>m</i>utation") or a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> ("<i>s</i>ingle <i>m</i>utation"). These terms do not specify if the pathogenic variant is <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> or somatic (see <a href="#cebpa-aml.Molecular_Pathogenesis">Molecular Pathogenesis</a>).</p><p>Molecular testing approaches include <b>single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b> and use of a <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>CEBPA</i> is performed in a non-leukemic specimen.</div><div class="half_rhythm">Note: (1) Testing for a <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> should not be performed on blood or bone marrow during active AML. Testing an uninvolved specimen, such as cells obtained by buccal swab/saliva, skin biopsy, or cultured dendritic cells, is imperative. (2) It should be noted that <i>CEBPA</i> pathogenic variants are found in the leukemic cells of approximately 9% of persons with AML (with <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> and <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants in similar proportions) [<a class="bk_pop" href="#cebpa-aml.REF.green.2010.2739">Green et al 2010</a>, <a class="bk_pop" href="#cebpa-aml.REF.dufour.2010.570">Dufour et al 2010</a>, <a class="bk_pop" href="#cebpa-aml.REF.fasan.2014.794">Fasan et al 2014</a>]. However, few of these individuals have a germline <i>CEBPA</i> pathogenic variant. (3) Testing of blood or bone marrow during complete remission from AML may also be performed to detect a <a class="def" href="/books/n/gene/glossary/def-item/germline-variant/">germline variant</a>. The percentage of residual leukemic cells in remission samples is negligible, ensuring that somatic variants are not falsely classified as germline variants.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>CEBPA</i> and other genes of interest (see <a href="#cebpa-aml.Differential_Diagnosis">Differential Diagnosis</a>) may also be considered, although care should be taken to ensure that coverage is adequate (due to the high GC content of the <a class="def" href="/books/n/gene/glossary/def-item/coding-region/">coding region</a>: 75%) and that large insertions, such as those targeting the C terminal, are accurately detected with high-throughput methods. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul><div id="cebpa-aml.T.molecular_genetic_testing_us" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>CEBPA</i>-Associated Familial Acute Myeloid Leukemia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47457/table/cebpa-aml.T.molecular_genetic_testing_us/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cebpa-aml.T.molecular_genetic_testing_us_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cebpa-aml.T.molecular_genetic_testing_us_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_cebpa-aml.T.molecular_genetic_testing_us_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_cebpa-aml.T.molecular_genetic_testing_us_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_cebpa-aml.T.molecular_genetic_testing_us_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CEBPA</i>
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</td><td headers="hd_h_cebpa-aml.T.molecular_genetic_testing_us_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_cebpa-aml.T.molecular_genetic_testing_us_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100% (14/14 families) <sup>4, 5</sup></td></tr><tr><td headers="hd_h_cebpa-aml.T.molecular_genetic_testing_us_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>6</sup></td><td headers="hd_h_cebpa-aml.T.molecular_genetic_testing_us_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>7</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="cebpa-aml.TF.1.1"><p class="no_margin">See <a href="/books/NBK47457/#cebpa-aml.molgen.TA">Table A. Genes and Databases</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> and protein.</p></div></dd><dt>2. </dt><dd><div id="cebpa-aml.TF.1.2"><p class="no_margin">See <a href="#cebpa-aml.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>.</p></div></dd><dt>3. </dt><dd><div id="cebpa-aml.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>4. </dt><dd><div id="cebpa-aml.TF.1.4"><p class="no_margin">Sequencing of the <a class="def" href="/books/n/gene/glossary/def-item/coding-region/">coding region</a> does not detect putative partial or complete <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions or variants in promoter regions. To date, however, no such <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> variants have been reported as causative of <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML.</p></div></dd><dt>5. </dt><dd><div id="cebpa-aml.TF.1.5"><p class="no_margin"><a class="bk_pop" href="#cebpa-aml.REF.smith.2004.2403">Smith et al [2004]</a>, <a class="bk_pop" href="#cebpa-aml.REF.sellick.2005.1276">Sellick et al [2005]</a>, <a class="bk_pop" href="#cebpa-aml.REF.pabst.2008.5088">Pabst et al [2008]</a>, <a class="bk_pop" href="#cebpa-aml.REF.renneville.2009.804">Renneville et al [2009]</a>, <a class="bk_pop" href="#cebpa-aml.REF.nanri.2010.237">Nanri et al [2010]</a>, <a class="bk_pop" href="#cebpa-aml.REF.stelljes.2011.1209">Stelljes et al [2011]</a>, <a class="bk_pop" href="#cebpa-aml.REF.taskesen.2011.2469">Taskesen et al [2011]</a>, <a class="bk_pop" href="#cebpa-aml.REF.xiao.2011.5257">Xiao et al [2011]</a>, <a class="bk_pop" href="#cebpa-aml.REF.debeljak.2013.e73">Debeljak et al [2013]</a>, <a class="bk_pop" href="#cebpa-aml.REF.tawana.2015.1214">Tawana et al [2015]</a>, <a class="bk_pop" href="#cebpa-aml.REF.pathak.2016.846">Pathak et al [2016]</a>, <a class="bk_pop" href="#cebpa-aml.REF.yan.2016.652">Yan et al [2016]</a>, <a class="bk_pop" href="#cebpa-aml.REF.mendoza.2021.1251">Mendoza et al [2021]</a></p></div></dd><dt>6. </dt><dd><div id="cebpa-aml.TF.1.6"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications.</p></div></dd><dt>7. </dt><dd><div id="cebpa-aml.TF.1.7"><p class="no_margin">No data on detection rate of <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> are available.</p></div></dd></dl></div></div></div></div></div><div id="cebpa-aml.Clinical_Characteristics"><h2 id="_cebpa-aml_Clinical_Characteristics_">Clinical Characteristics</h2><div id="cebpa-aml.Clinical_Description"><h3>Clinical Description</h3><p>To date, fourteen families with <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> acute myeloid leukemia (AML) have been reported [<a class="bk_pop" href="#cebpa-aml.REF.smith.2004.2403">Smith et al 2004</a>, <a class="bk_pop" href="#cebpa-aml.REF.sellick.2005.1276">Sellick et al 2005</a>, <a class="bk_pop" href="#cebpa-aml.REF.pabst.2008.5088">Pabst et al 2008</a>, <a class="bk_pop" href="#cebpa-aml.REF.renneville.2009.804">Renneville et al 2009</a>, <a class="bk_pop" href="#cebpa-aml.REF.nanri.2010.237">Nanri et al 2010</a>, <a class="bk_pop" href="#cebpa-aml.REF.stelljes.2011.1209">Stelljes et al 2011</a>, <a class="bk_pop" href="#cebpa-aml.REF.taskesen.2011.2469">Taskesen et al 2011</a>, <a class="bk_pop" href="#cebpa-aml.REF.xiao.2011.5257">Xiao et al 2011</a>, <a class="bk_pop" href="#cebpa-aml.REF.debeljak.2013.e73">Debeljak et al 2013</a>, <a class="bk_pop" href="#cebpa-aml.REF.tawana.2015.1214">Tawana et al 2015</a>, <a class="bk_pop" href="#cebpa-aml.REF.pathak.2016.846">Pathak et al 2016</a>, <a class="bk_pop" href="#cebpa-aml.REF.yan.2016.652">Yan et al 2016</a>, <a class="bk_pop" href="#cebpa-aml.REF.mendoza.2021.1251">Mendoza et al 2021</a>], the majority of which manifest a highly penetrant (>80%) AML <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. More recently, <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> pathogenic variants located outside of the N terminal appear less penetrant, with approximately 50% of individuals with a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> germline <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> developing AML. Given the limited number of family members tested in historical studies, it is possible that the true <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> of AML may vary [<a class="bk_pop" href="#cebpa-aml.REF.pabst.2009.5303">Pabst & Mueller 2009</a>].</p><p>The age of onset of <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML is variable, but appears to be earlier than in <a class="def" href="/books/n/gene/glossary/def-item/sporadic/">sporadic</a> AML. Disease onset has been reported in persons as young as 1.8 years [<a class="bk_pop" href="#cebpa-aml.REF.debeljak.2013.e73">Debeljak et al 2013</a>] and older than 45 years [<a class="bk_pop" href="#cebpa-aml.REF.pabst.2008.5088">Pabst et al 2008</a>]. By contrast, the median age at diagnosis of persons with sporadic AML is 65 years.</p><p>Individuals commonly present with AML (of French-American-British subtypes M1, M2 or M4) following the acquisition of a somatic <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and additional somatic pathogenic variants, frequently involving <i>GATA2</i> (zinc finger 1), <i>WT1</i>, <i>TET2</i>, <i>EZH2</i>, and <i>NRAS</i> [<a class="bk_pop" href="#cebpa-aml.REF.tawana.2015.1214">Tawana et al 2015</a>].</p><p>From an analysis of ten pedigrees with <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML, the disease follows a course similar to <a class="def" href="/books/n/gene/glossary/def-item/sporadic/">sporadic</a> AML with <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>CEBPA</i> pathogenic variants (<i>CEBPA</i>dm)<i>.</i> The prognosis of individuals with familial AML appears to be favorable, with ten-year overall survival (OS) reaching 67%, compared to 54% OS in younger adults with sporadic AML associated with two <i>CEBPA</i> pathogenic variants and 29% OS with sporadic AML associated with a single <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> [<a class="bk_pop" href="#cebpa-aml.REF.tawana.2015.1214">Tawana et al 2015</a>].</p><p>Individuals with <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML who have been cured of their initial disease may be at greater risk of developing recurrent, independent leukemic episodes that are characterized by a different somatic <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> from that observed in the original tumor clone. This phenomenon contrasts with relapse in individuals with <a class="def" href="/books/n/gene/glossary/def-item/sporadic/">sporadic</a> AML, where <i>CEBPA</i> pathogenic variants are stable throughout the disease course [<a class="bk_pop" href="#cebpa-aml.REF.tiesmeier.2003.413">Tiesmeier et al 2003</a>, <a class="bk_pop" href="#cebpa-aml.REF.shih.2006.604">Shih et al 2006</a>, <a class="bk_pop" href="#cebpa-aml.REF.hollink.2011.384">Hollink et al 2011</a>].</p></div><div id="cebpa-aml.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>To date, the majority of <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> pathogenic variants are frameshift variants located in the N terminal of the <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> (preceding the internal start codon, located at codon 120).</p></div><div id="cebpa-aml.Penetrance"><h3>Penetrance</h3><p>Analysis of pedigrees reported to date suggests that <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> pathogenic variants exhibit high <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> for the development of AML [<a class="bk_pop" href="#cebpa-aml.REF.nickels.2013.254">Nickels et al 2013</a>, <a class="bk_pop" href="#cebpa-aml.REF.tawana.2015.1214">Tawana et al 2015</a>]. The penetrance of pathogenic variants may vary within and between families; data from ten families with germline <i>CEBPA</i> pathogenic variants affecting the N terminal (preceding the internal start codon, located at codon 120) revealed that more than 80% of confirmed or presumed obligate adult heterozygotes have developed disease to date [<a class="bk_pop" href="#cebpa-aml.REF.tawana.2015.1214">Tawana et al 2015</a>]. Germline <i>CEBPA</i> pathogenic variants located outside of the N terminal (e.g., within the transactivation or leucine zipper domains) appear less penetrant, with approximately 50% of individuals with a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> germline <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> developing AML [<a class="bk_pop" href="#cebpa-aml.REF.pathak.2016.846">Pathak et al 2016</a>, <a class="bk_pop" href="#cebpa-aml.REF.mendoza.2021.1251">Mendoza et al 2021</a>].</p></div><div id="cebpa-aml.Nomenclature"><h3>Nomenclature</h3><p>International recognition of inherited hematologic malignancies has grown significantly following the WHO classification in 2016, which incorporated myeloid neoplasms associated with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>ANKRD26</i>, <i>CEBPA</i>, <a href="/books/n/gene/ddx41-mds/"><i>DDX41</i></a>, <i>GATA2</i>, and <a href="/books/n/gene/runx1/"><i>RUNX1</i></a> pathogenic variants [<a class="bk_pop" href="#cebpa-aml.REF.arber.2016.2391">Arber et al 2016</a>]. The WHO classification also defined AML with <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>CEBPA</i> pathogenic variants (<i>CEBPA</i>dm [<i>CEBPA</i> double-mutated]) as a distinct prognostic entity. Of note, there was no distinction between <a class="def" href="/books/n/gene/glossary/def-item/sporadic/">sporadic</a> and <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML within this category.</p></div><div id="cebpa-aml.Prevalence"><h3>Prevalence</h3><p><i>CEBPA-</i>associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML is very rare, with only fourteen pedigrees reported [<a class="bk_pop" href="#cebpa-aml.REF.smith.2004.2403">Smith et al 2004</a>, <a class="bk_pop" href="#cebpa-aml.REF.sellick.2005.1276">Sellick et al 2005</a>, <a class="bk_pop" href="#cebpa-aml.REF.pabst.2008.5088">Pabst et al 2008</a>, <a class="bk_pop" href="#cebpa-aml.REF.renneville.2009.804">Renneville et al 2009</a>, <a class="bk_pop" href="#cebpa-aml.REF.nanri.2010.237">Nanri et al 2010</a>, <a class="bk_pop" href="#cebpa-aml.REF.stelljes.2011.1209">Stelljes et al 2011</a>, <a class="bk_pop" href="#cebpa-aml.REF.taskesen.2011.2469">Taskesen et al 2011</a>, <a class="bk_pop" href="#cebpa-aml.REF.xiao.2011.5257">Xiao et al 2011</a>, <a class="bk_pop" href="#cebpa-aml.REF.debeljak.2013.e73">Debeljak et al 2013</a>, <a class="bk_pop" href="#cebpa-aml.REF.tawana.2015.1214">Tawana et al 2015</a>, <a class="bk_pop" href="#cebpa-aml.REF.pathak.2016.846">Pathak et al 2016</a>, <a class="bk_pop" href="#cebpa-aml.REF.mendoza.2021.1251">Mendoza et al 2021</a>].</p><p><a class="bk_pop" href="#cebpa-aml.REF.taskesen.2011.2469">Taskesen et al [2011]</a> identified a <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in five of 71 individuals (7%); two of the five had a family history of AML.</p></div></div><div id="cebpa-aml.Genetically_Related_Allelic_Di"><h2 id="_cebpa-aml_Genetically_Related_Allelic_Di_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in <i>CEBPA</i>.</p><p>Note: Sporadic <i>CEBPA-</i>associated acute myeloid leukemia (AML) is defined as AML in which a somatic <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>(s) is acquired in leukemic cells alone and not in the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> (see <a href="#cebpa-aml.Molecular_Genetics">Molecular Genetics</a>).</p></div><div id="cebpa-aml.Differential_Diagnosis"><h2 id="_cebpa-aml_Differential_Diagnosis_">Differential Diagnosis</h2><p>The differential diagnosis for <i>CEBPA-</i>associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> acute myeloid leukemia (AML) includes the following:</p><ul><li class="half_rhythm"><div>Hereditary disorders associated with an increased risk of myeloid malignancy (e.g., <a href="/books/n/gene/runx1/"><i>RUNX1</i> familial platelet disorder with associated myeloid malignancy</a>, <a href="/books/n/gene/ddx41-mds/"><i>DDX41</i>-associated familial myelodysplastic syndrome and acute myeloid leukemia</a>)</div></li><li class="half_rhythm"><div>Sporadic AML with somatic <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>(s)</div></li><li class="half_rhythm"><div>AML secondary to environmental exposures (e.g., benzene, radiation, chemotherapy)</div></li></ul><p>Note: AML is a relatively rare disorder (~13,300 cases/year in the US); therefore, the more affected individuals in a family (and the closer the relationships), the greater the likelihood of a common cause (i.e., a heritable predisposition or a common exposure) [<a class="bk_pop" href="#cebpa-aml.REF.owen.2008.123">Owen et al 2008</a>].</p></div><div id="cebpa-aml.Management"><h2 id="_cebpa-aml_Management_">Management</h2><div id="cebpa-aml.Evaluations_Following_Initial"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs of an individual newly diagnosed with <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> acute myeloid leukemia (AML), the evaluations summarized in <a href="/books/NBK47457/table/cebpa-aml.T.recommended_evaluations_foll/?report=objectonly" target="object" rid-ob="figobcebpaamlTrecommendedevaluationsfoll">Table 2</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="cebpa-aml.T.recommended_evaluations_foll" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <i>CEBPA</i>-Associated Familial Acute Myeloid Leukemia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47457/table/cebpa-aml.T.recommended_evaluations_foll/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cebpa-aml.T.recommended_evaluations_foll_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>AYA/pediatric</b>
|
||
<br />
|
||
<b>AML</b>
|
||
</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Management of younger persons to be directed by relevant specialist teams (e.g., AYA or pediatric hematologists)</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>AML /</b>
|
||
<br />
|
||
<b>Assessment</b>
|
||
<br />
|
||
<b>for suitable</b>
|
||
<br />
|
||
<b>HSCT donor</b>
|
||
</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">HLA typing & virology tests (hepatitis A, B, C, & HIV)</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><i>CEBPA</i> site-specific testing of family members at risk using either of the following:
|
||
<ul><li class="half_rhythm"><div>Buccal, salivary, or skin DNA</div></li><li class="half_rhythm"><div>Peripheral blood DNA in persons w/no history of preceding hematologic disease & normal CBC</div></li></ul>
|
||
</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Family members w/o an inherited <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> may be offered HLA typing to assess their compatibility for stem cell donation to their affected relative.</td></tr><tr><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Fertility</b>
|
||
</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Provide info re oocyte & sperm cryopreservation to persons of childbearing potential</div></li><li class="half_rhythm"><div>Women: negative pregnancy test prior to commencing therapy</div></li></ul>
|
||
</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>CNS AML</b>
|
||
</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">LP if symptoms suggest CNS disease.</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The timing of LP in AML is controversial.</td></tr><tr><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Treatment-</b>
|
||
<br />
|
||
<b>related heart</b>
|
||
<br />
|
||
<b>disease</b>
|
||
</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiac scan in persons w/personal history of (or signs & symptoms suspicious for) heart disease & in those who have received previous anthracycline therapy</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic</b>
|
||
<br />
|
||
<b>counseling</b>
|
||
</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>By genetics professionals <sup>1</sup></div></li><li class="half_rhythm"><div>Obtain a detailed family history & identify relatives who are obligate heterozygotes or potential heterozygotes for a <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> & thus at risk for <i>CEBPA</i>-assoc <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML.</div></li></ul>
|
||
</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of <i>CEBPA</i>-assoc <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML in facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family support/</b>
|
||
<br />
|
||
<b>resources</b>
|
||
</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess:
|
||
<ul><li class="half_rhythm"><div>Use of community or <a href="#cebpa-aml.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a>;</div></li><li class="half_rhythm"><div>Need for social work involvement for parental support;</div></li><li class="half_rhythm"><div>Need for home nursing referral.</div></li></ul>
|
||
</td><td headers="hd_h_cebpa-aml.T.recommended_evaluations_foll_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AYA = adolescent and young adult; AML = acute myeloid leukemia; CBC = complete blood count; CNS = central nervous system; HLA = human leukocyte antigen; HSCT = hematopoietic stem cell transplantation; LP = lumbar puncture; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a></p></div></dd><dt>1. </dt><dd><div id="cebpa-aml.TF.2.1"><p class="no_margin">Medical geneticist, certified genetic counselor, or certified advanced genetic nurse</p></div></dd></dl></div></div></div></div><div id="cebpa-aml.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Management of <i>CEBPA-</i>associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML does not differ from that of <a class="def" href="/books/n/gene/glossary/def-item/sporadic/">sporadic</a> <i>CEBPA-</i>associated AML [<a class="bk_pop" href="#cebpa-aml.REF.d_hner.2017.424">Döhner et al 2017</a>] (see also <a href="https://www.nccn.org/professionals/physician_gls/default.aspx#site" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCCN Clinical Practice Guidelines in Oncology</a>; no-fee registration and login required).</p><p>Treatment usually includes cytarabine/anthracycline-based induction and cytarabine-based consolidation chemotherapy with or without hematopoietic stem cell transplantation (HSCT) according to clinical, <a class="def" href="/books/n/gene/glossary/def-item/cytogenetic/">cytogenetic</a>, and molecular risk. Specific treatment strategies are based on characteristics of the individual, response to chemotherapy, treatment setting, and protocol (if the individual is enrolled in a clinical trial). Note: Whenever possible, persons with AML should be treated as part of a clinical trial protocol.</p><p>Germline variants should be investigated and excluded in donors prior to consideration of HSCT using sib/related donors.</p><p>Supportive care includes blood products such as red blood cell and platelet transfusions as needed and treatment of infections with antibiotics.</p><p>Prophylactic antibiotics and antifungal agents are administered during periods of severe neutropenia including the consolidation and post-transplantation periods (<a href="https://www.nccn.org/professionals/physician_gls/default.aspx#site" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCCN Clinical Practice Guidelines in Oncology</a>; no-fee registration and login required).</p><p>Relapses are treated with cytarabine-based salvage chemotherapy followed by allogeneic HSCT (if a suitable donor is available and if cure is the intent of treatment).</p></div><div id="cebpa-aml.Surveillance"><h3>Surveillance</h3><p><b>Affected individuals.</b> Surveillance for <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML is similar to that for other forms of AML. There are no generally accepted minimal residual disease (MRD) markers in <i>CEBPA-</i>associated AML.</p><p>Individuals are monitored and evaluated in accordance with administered treatment, clinical course, symptoms, and protocol, if enrolled in clinical trials. When complete remission is achieved and intensification therapy is complete, individuals are monitored with:</p><ul><li class="half_rhythm"><div>CBC and platelet counts every one to three months for two years with the frequency decreasing to every three to six months for up to five years;</div></li><li class="half_rhythm"><div>Bone marrow aspiration when cytopenia and/or an abnormal peripheral blood smear are present.</div></li></ul><p>Note: The use of flow cytometry for MRD monitoring is controversial.</p><p>Individuals with a <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> who are cured of their initial disease episode may be at risk for new leukemic episodes, often occurring after a prolonged period of remission (>3 years post presentation) [<a class="bk_pop" href="#cebpa-aml.REF.pabst.2009.1343">Pabst et al 2009</a>, <a class="bk_pop" href="#cebpa-aml.REF.tawana.2015.1214">Tawana et al 2015</a>]. In light of these data, lifelong clinical surveillance is warranted to ensure prompt recognition and appropriate management of disease recurrence. Repeat testing of <i>CEBPA</i> in tumor DNA at AML recurrence is important to help distinguish conventional relapse from new, independent leukemic episodes.</p><p><b>Asymptomatic individuals</b> with a <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>:</p><ul><li class="half_rhythm"><div>CBC every six to 12 months</div></li><li class="half_rhythm"><div>Bone marrow examination for those with CBC abnormalities</div></li></ul></div><div id="cebpa-aml.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Use of sib or related donors for HSCT without prior assessment of the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in the donor should be avoided.</p></div><div id="cebpa-aml.Evaluation_of_Relatives_at_Ris"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from clinical monitoring. Clinical monitoring may enable earlier diagnosis (and treatment) of AML, hence minimizing the risks associated with delayed presentation (e.g., severe anemia, neutropenic sepsis, and severe hemorrhage).</p><p>Note:</p><ul><li class="half_rhythm"><div>There are currently no preemptive treatments available for asymptomatic individuals who have a <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>To date, all individuals with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> pathogenic variants have presented with overt AML without any preceding blood count abnormalities or myelodysplasia; this is in contrast with other <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> leukemia syndromes such as those associated with germline <i>RUNX1</i> or <i>GATA2</i> pathogenic variants [<a class="bk_pop" href="#cebpa-aml.REF.tawana.2017.87">Tawana et al 2017</a>].</div></li></ul><p>See <a href="#cebpa-aml.Related_Genetic_Counseling_Iss">Genetic Counseling</a> for issues related to testing of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="cebpa-aml.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="cebpa-aml.Genetic_Counseling"><h2 id="_cebpa-aml_Genetic_Counseling_">Genetic Counseling</h2><p>
|
||
<i>Genetic counseling is the process of providing individuals and families with
|
||
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
||
make informed medical and personal decisions. The following section deals with genetic
|
||
risk assessment and the use of family history and genetic testing to clarify genetic
|
||
status for family members; it is not meant to address all personal, cultural, or
|
||
ethical issues that may arise or to substitute for consultation with a genetics
|
||
professional</i>. —ED.</p><div id="cebpa-aml.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Predisposition to <i>CEBPA-</i>associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> acute myeloid leukemia (AML) is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner.</p></div><div id="cebpa-aml.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>Most individuals diagnosed with <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML inherited a <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> from an affected parent.</div></li><li class="half_rhythm"><div>In rare cases, a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> may have a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> appears to be the only affected family member (i.e., a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case), <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> is recommended for the parents of the proband to confirm their genetic status and to allow reliable <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> counseling.</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is not identified in either parent, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>The <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. Note: A pathogenic variant is reported as "<i>de novo</i>" if: (1) the pathogenic variant found in the proband is not detected in parental DNA; and (2) parental identity testing has confirmed biological maternity and paternity. If parental identity testing is not performed, the variant is reported as "assumed <i>de novo</i>" [<a class="bk_pop" href="#cebpa-aml.REF.richards.2015.405">Richards et al 2015</a>].</div></li><li class="half_rhythm"><div>The <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> inherited a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> from a parent with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> (or somatic and germline) <a class="def" href="/books/n/gene/glossary/def-item/mosaicism/">mosaicism</a>. Note: Testing of parental leukocyte DNA may not detect all instances of <a class="def" href="/books/n/gene/glossary/def-item/somatic-mosaicism/">somatic mosaicism</a>.</div></li></ul></li><li class="half_rhythm"><div>The family history of some individuals diagnosed with <i>CEBPA-</i>associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML may appear to be negative because of early death of a parent before the onset of AML or late onset of AML in a parent. Therefore, an apparently negative family history cannot be verified unless <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> has demonstrated that neither parent is <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</div></li></ul><p><b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to the sibs of the proband depends on the genetic status of the proband’s parents:</p><ul><li class="half_rhythm"><div>If a parent of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has the <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%.</div></li><li class="half_rhythm"><div>The likelihood that a sib who inherits a <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> will develop AML varies within and between families (ranging from ~50% to >80%) and appears to be significantly influenced by the site of the pathogenic variant (see <a href="#cebpa-aml.Penetrance">Penetrance</a>).</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> cannot be detected in the leukocyte DNA of either parent, the <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> to sibs is estimated to be 1% because of the theoretic possibility of parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> [<a class="bk_pop" href="#cebpa-aml.REF.rahbari.2016.126">Rahbari et al 2016</a>].</div></li><li class="half_rhythm"><div>If the parents have not been tested for the <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> but are clinically unaffected, sibs are still at increased risk for <i>CEBPA-</i>associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML because (1) the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variant may demonstrate differences in disease manifestation and latency in a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> parent, and (2) because of the theoretic possibility of parental somatic/<a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>.</div></li></ul><p><b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Each child of an individual with <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML has a 50% chance of inheriting the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p><p><b>Other family members.</b> The risk to other family members of inheriting the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> depends on the genetic status of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents: if a parent has the <i>CEBPA</i> pathogenic variant, his or her family members may be at risk.</p></div><div id="cebpa-aml.Related_Genetic_Counseling_Iss"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#cebpa-aml.Evaluation_of_Relatives_at_Ris">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p><b>Testing of at-risk asymptomatic family members.</b> If a <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified in a family member with AML, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> may be offered to at-risk family members in order to determine the need for clinical surveillance (see <a href="#cebpa-aml.Evaluation_of_Relatives_at_Ris">Evaluation of Relatives at Risk</a>).</p><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk in offspring of persons with known <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML is before pregnancy. (Note: Molecular genetic <i>CEBPA</i> testing for the purpose of family planning is not recommended for individuals who develop AML in the absence of a molecular diagnosis of <i>CEBPA</i>-associated familial AML.)</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to young adults who have a molecular diagnosis of <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML or who are at risk of having inherited a familial <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li></ul></div><div id="cebpa-aml.Prenatal_Testing_and_Preimplan"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once a <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified in an affected family member, <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> for a pregnancy at increased risk and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> for <i>CEBPA</i>-associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a>. While use of prenatal testing is a personal decision, discussion of these issues may be helpful.</p></div></div><div id="cebpa-aml.Resources"><h2 id="_cebpa-aml_Resources_">Resources</h2><p>
|
||
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
||
support organizations and/or registries for the benefit of individuals with this disorder
|
||
and their families. GeneReviews is not responsible for the information provided by other
|
||
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/">here</a>.</i></p>
|
||
<ul><li class="half_rhythm"><div>
|
||
<b>MedlinePlus</b>
|
||
</div><div>
|
||
<a href="https://medlineplus.gov/genetics/condition/familial-acute-myeloid-leukemia-with-mutated-cebpa/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Familial acute myeloid leukemia with mutated CEBPA</a>
|
||
</div></li></ul>
|
||
</div><div id="cebpa-aml.Molecular_Genetics"><h2 id="_cebpa-aml_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div id="cebpa-aml.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>CEBPA-Associated Familial Acute Myeloid Leukemia (AML): Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47457/table/cebpa-aml.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cebpa-aml.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_cebpa-aml.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_cebpa-aml.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_cebpa-aml.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_cebpa-aml.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_cebpa-aml.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_cebpa-aml.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/1050" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>CEBPA</i>
|
||
</a>
|
||
</td><td headers="hd_b_cebpa-aml.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=1050" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">19q13<wbr style="display:inline-block"></wbr>.11</a>
|
||
</td><td headers="hd_b_cebpa-aml.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P49715" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CCAAT/enhancer-binding protein alpha</a>
|
||
</td><td headers="hd_b_cebpa-aml.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CEBPA" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CEBPA</a>
|
||
</td><td headers="hd_b_cebpa-aml.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CEBPA[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CEBPA</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="cebpa-aml.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="cebpa-aml.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for CEBPA-Associated Familial Acute Myeloid Leukemia (AML) (<a href="/omim/116897,601626" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47457/table/cebpa-aml.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cebpa-aml.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/116897" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">116897</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CCAAT/ENHANCER-BINDING PROTEIN, ALPHA; CEBPA</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/601626" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">601626</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEUKEMIA, ACUTE MYELOID; AML</td></tr></tbody></table></div></div><div id="cebpa-aml.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>CEBPA</i> encodes the CCAAT/enhancer-binding protein alpha (C/EBPα), a <a class="def" href="/books/n/gene/glossary/def-item/transcription-factor/">transcription factor</a> that plays a key role in granulocyte development. A detailed review of the role of C/EBPα in human cancer has been published [<a class="bk_pop" href="#cebpa-aml.REF.koschmieder.2009.619">Koschmieder et al 2009</a>]. The role of mutation of <i>CEBPA</i> in the formation of acute myeloid leukemia (AML) is not well understood and is subject to ongoing research with several established mouse models simulating <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> N-terminal frameshift pathogenic variants [<a class="bk_pop" href="#cebpa-aml.REF.kirstetter.2008.299">Kirstetter et al 2008</a>], combined N- and C-terminal pathogenic variants [<a class="bk_pop" href="#cebpa-aml.REF.bereshchenko.2009.390">Bereshchenko et al 2009</a>], or conditional loss of C/EBPα [<a class="bk_pop" href="#cebpa-aml.REF.ye.2013.385">Ye et al 2013</a>].</p><p>Initiation of translation at two <a class="def" href="/books/n/gene/glossary/def-item/in-frame/">in-frame</a> AUG start codons (nucleotides 151-153 and 508-510) results in two C/EBPα protein <a class="def" href="/books/n/gene/glossary/def-item/isoforms/">isoforms</a> with different lengths (see <a href="/books/NBK47457/#cebpa-aml.molgen.TA">Table A</a>, <b>Gene</b>). When translation initiates from the AUG at nucleotides 151-153, a 42-kd (also known as C/EBP-42) isoform a <a class="def" href="/books/n/gene/glossary/def-item/transcription-factor/">transcription factor</a> is produced (<a href="https://www.ncbi.nlm.nih.gov/protein/NP_004355.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_004355.2</a>). The full-length 42-kd protein contains two distinct transactivation domains (that mediate contact with transcriptional apparatus), a C-terminal basic region (DNA-binding), and a leucine zipper for dimerization. Alternatively, when translation initiates from the alternative start site at AUG at nucleotides 508-510, a 30-kd (also known as C/EBP-30) isoform b is produced that lacks the first transactivation <a class="def" href="/books/n/gene/glossary/def-item/domain/">domain</a> and impairs interaction with the transcriptional apparatus mediating cell-cycle progression (<a href="https://www.ncbi.nlm.nih.gov/protein/NP_001272758.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001272758.1</a>). While both isoforms are normally translated, the 42-kd isoform is more abundant.</p><p>All reported <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants are small deletions, duplications, or insertions before codon 120. These result in a frameshift causing premature truncation at the N-terminal region of the full-length C/EBPα protein, with preservation of the 30-kd isoform. The 30-kd isoform is believed to inhibit the action of the 42-kd isoform in a <a class="def" href="/books/n/gene/glossary/def-item/dominant-negative/">dominant-negative</a> manner.</p><p><b>Mechanism of disease causation.</b> Germline <i>CEBPA</i> pathogenic variants cause premature termination of the full-length C/EBPα protein, with preservation of the 30-kd isoform. The 30-kd isoform may inhibit the action of the normal 42-kd isoform (encoded by the remaining normal <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>) in a <a class="def" href="/books/n/gene/glossary/def-item/dominant-negative/">dominant-negative</a> manner. The acquisition of somatic <a class="def" href="/books/n/gene/glossary/def-item/in-frame/">in-frame</a> insertions and deletions within the highly conserved C-terminal domains interferes with dimerization and DNA binding. The combination of N- and C-terminal pathogenic variants are thought to disrupt homo- and heterodimerization, cell cycle arrest, and differentiation [<a class="bk_pop" href="#cebpa-aml.REF.pabst.2009.5303">Pabst & Mueller 2009</a>].</p><p><b><i>CEBPA</i>-specific laboratory technical considerations.</b>
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<i>CEBPA</i> is a single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>; the GC-rich <a class="def" href="/books/n/gene/glossary/def-item/coding-region/">coding region</a> can interfere with <a class="def" href="/books/n/gene/glossary/def-item/pcr/">PCR</a> amplification and care should be taken to optimize diagnostic tests fully for sensitive and accurate detection of all variants.</p><div id="cebpa-aml.T.notable_familial_acute_myelo" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Notable Familial Acute Myeloid Leukemia-Associated <i>CEBPA</i> Germline Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47457/table/cebpa-aml.T.notable_familial_acute_myelo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cebpa-aml.T.notable_familial_acute_myelo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference</th></tr></thead><tbody><tr><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_1" rowspan="9" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_004364.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_004364<wbr style="display:inline-block"></wbr>.5</a>
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<br />
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<p>
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_004355.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_004355<wbr style="display:inline-block"></wbr>.2</a>
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</p>
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</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.68delC</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Pro23ArgfsTer137</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a class="bk_pop" href="#cebpa-aml.REF.smith.2004.2403">Smith et al [2004]</a>
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</td></tr><tr><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.68dupC</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.His24AlafsTer84</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bk_pop" href="#cebpa-aml.REF.sellick.2005.1276">Sellick et al [2005]</a>, <a class="bk_pop" href="#cebpa-aml.REF.renneville.2009.804">Renneville et al [2009]</a>, <a class="bk_pop" href="#cebpa-aml.REF.tawana.2015.1214">Tawana et al [2015]</a></td></tr><tr><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.141delC</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ala48ProfsTer112</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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||
<a class="bk_pop" href="#cebpa-aml.REF.pabst.2008.5088">Pabst et al [2008]</a>
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||
</td></tr><tr><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.147_165del19</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Glu50AlafsTer104</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a class="bk_pop" href="#cebpa-aml.REF.debeljak.2013.e73">Debeljak et al [2013]</a>
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||
</td></tr><tr><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.158delG</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly53AlafsTer107</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_4" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">
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||
<a class="bk_pop" href="#cebpa-aml.REF.taskesen.2011.2469">Taskesen et al [2011]</a>
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||
</td></tr><tr><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.189delC</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Asp63GlufsTer97</td></tr><tr><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.314_315insT</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Phe106LeufsTer2</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a class="bk_pop" href="#cebpa-aml.REF.pabst.2008.5088">Pabst et al [2008]</a>
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||
</td></tr><tr><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.932A>C</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln311Pro</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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||
<a class="bk_pop" href="#cebpa-aml.REF.pathak.2016.846">Pathak et al [2016]</a>
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||
</td></tr><tr><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.442G>T</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Glu148Ter</td><td headers="hd_h_cebpa-aml.T.notable_familial_acute_myelo_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a class="bk_pop" href="#cebpa-aml.REF.mendoza.2021.1251">Mendoza et al [2021]</a>
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</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></div></div></div></div><div id="cebpa-aml.Cancer_and_Benign_Tumors"><h3>Cancer and Benign Tumors</h3><p>
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||
<b>Somatic <i>CEBPA</i> pathogenic variants</b>
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||
</p><ul><li class="half_rhythm"><div><b><i>CEBPA-</i>associated <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> AML.</b> The leukemic cells of most individuals with <i>CEBPA-</i>associated familial AML are <a class="def" href="/books/n/gene/glossary/def-item/compound-heterozygous/">compound heterozygous</a>. In addition to the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in the N-terminal region, the leukemic cells commonly acquire somatic C-terminal <a class="def" href="/books/n/gene/glossary/def-item/in-frame/">in-frame</a> pathogenic variant(s). Such variants disrupt the basic region and leucine zipper, impairing DNA binding as well as homo- and heterodimerization with other CEBP proteins and/or DNA binding [<a class="bk_pop" href="#cebpa-aml.REF.pabst.2007.6829">Pabst & Mueller 2007</a>, <a class="bk_pop" href="#cebpa-aml.REF.pabst.2009.5303">Pabst & Mueller 2009</a>].</div></li><li class="half_rhythm"><div><b>Sporadic <i>CEBPA-</i>associated AML.</b> This is defined as AML in which a somatic <i>CEBPA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>(s) is acquired in leukemic cells alone and not in the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a>. In 45%-55% of all persons with <a class="def" href="/books/n/gene/glossary/def-item/sporadic/">sporadic</a> <i>CEBPA</i>-associated AML<i>,</i> two pathogenic <i>CEBPA</i> variants are detected (<i>CEBPA</i>dm); most frequently, a frameshift N-terminal variant is combined with a C-terminal <a class="def" href="/books/n/gene/glossary/def-item/in-frame/">in-frame</a> <a class="def" href="/books/n/gene/glossary/def-item/insertion/">insertion</a> or <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> [<a class="bk_pop" href="#cebpa-aml.REF.green.2010.2739">Green et al 2010</a>, <a class="bk_pop" href="#cebpa-aml.REF.fasan.2014.794">Fasan et al 2014</a>].</div></li><li class="half_rhythm"><div><i>CEBPA</i> pathogenic variants have not been detected in solid tumors, although deregulation of <i>CEBPA</i> expression has been reported in liver, lung, and breast cancer, suggesting alternative mechanisms of abrogation [<a class="bk_pop" href="#cebpa-aml.REF.louren_o.2017.5221">Lourenço & Coffer 2017</a>].</div></li></ul></div></div><div id="cebpa-aml.Chapter_Notes"><h2 id="_cebpa-aml_Chapter_Notes_">Chapter Notes</h2><div id="cebpa-aml.Author_History"><h3>Author History</h3><p>Jude Fitzgibbon, PhD (2016-present)<br />Roger D Klein, MD, JD; Cleveland Clinic (2010-2016)<br />Guido Marcucci, MD; Ohio State University (2010-2016)<br />Kiran Tawana, MBChB, FRCPath, PhD (2016-present)</p></div><div id="cebpa-aml.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>18 February 2021 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>28 April 2016 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>21 October 2010 (me) Review posted live</div></li><li class="half_rhythm"><div>30 December 2009 (rdk) Original submission</div></li></ul></div></div><div id="cebpa-aml.References"><h2 id="_cebpa-aml_References_">References</h2><div id="cebpa-aml.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="cebpa-aml.REF.arber.2016.2391">Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. <span><span class="ref-journal">Blood. </span>2016;<span class="ref-vol">127</span>:2391–405.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27069254" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27069254</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cebpa-aml.REF.bereshchenko.2009.390">Bereshchenko O, Mancini E, Moore S, Bilbao D, Månsson R, Luc S, Grover A, Jacobsen SE, Bryder D, Nerlov C. Hematopoietic stem cell expansion precedes the generation of committed myeloid leukemia-initiating cells in C/EBPalpha mutant AML. <span><span class="ref-journal">Cancer Cell. </span>2009;<span class="ref-vol">16</span>:390–400.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19878871" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19878871</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cebpa-aml.REF.debeljak.2013.e73">Debeljak M, Kitanovski L, Pajič T, Jazbec J. Concordant acute myeloblastic leukemia in monozygotic twins with germline and shared somatic mutations in the gene for CCAAT-enhancer-binding protein α with 13 years difference at onset. <span><span class="ref-journal">Haematologica. </span>2013;<span class="ref-vol">98</span>:e73–4.</span> [<a href="/pmc/articles/PMC3696596/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3696596</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23716546" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23716546</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cebpa-aml.REF.d_hner.2017.424">Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Löwenberg B, Bloomfield CD. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. <span><span class="ref-journal">Blood. </span>2017;<span class="ref-vol">129</span>:424–47.</span> [<a href="/pmc/articles/PMC5291965/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5291965</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27895058" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27895058</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cebpa-aml.REF.dufour.2010.570">Dufour A, Schneider F, Metzeler KH, Hoster E, Schneider S, Zellmeier E, Benthaus T, Sauerland MC, Berdel WE, Büchner T, Wörmann B, Braess J, Hiddemann W, Bohlander SK, Spiekermann K. Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome. <span><span class="ref-journal">J Clin Oncol. </span>2010;<span class="ref-vol">28</span>:570–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20038735" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20038735</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cebpa-aml.REF.fasan.2014.794">Fasan A, Haferlach C, Alpermann T, Jeromin S, Grossmann V, Eder C, Weissmann S, Dicker F, Kohlmann A, Schindela S, Kern W, Haferlach T, Schnittger S. The role of different genetic subtypes of CEBPA mutated AML. <span><span class="ref-journal">Leukemia. </span>2014;<span class="ref-vol">28</span>:794–803.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24056881" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24056881</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cebpa-aml.REF.green.2010.2739">Green CL, Koo KK, Hills RK, Burnett AK, Linch DC, Gale RE. Prognostic Significance of CEBPA Mutations in a large cohort of younger adult patients with acute myeloid leukemia: impact of double CEBPA mutations and the interaction with FLT3 and NPM1 mutations. <span><span class="ref-journal">J Clin Oncol. </span>2010;<span class="ref-vol">28</span>:2739–47.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20439648" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20439648</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cebpa-aml.REF.hollink.2011.384">Hollink IH, van den Heuvel-Eibrink MM, Arentsen-Peters ST, Zimmermann M, Peeters JK, Valk PJ, Balgobind BV, Sonneveld E, Kaspers GJ, de Bont ES, Trka J, Baruchel A, Creutzig U, Pieters R, Reinhardt D, Zwaan CM. 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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK47457/?report=reader">PubReader</a></li><li><a href="/books/NBK47457/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK47457" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK47457" style="display:none" title="Cite this Page"><div class="bk_tt">Tawana K, Fitzgibbon J. CEBPA-Associated Familial Acute Myeloid Leukemia (AML) 2010 Oct 21 [Updated 2021 Feb 18]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK47457/pdf/Bookshelf_NBK47457.pdf">PDF version of this page</a> (489K)</li><li><a href="#" class="toggle-glossary-link" title="Enable/disable links to the glossary">Disable Glossary Links</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this GeneReview</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#cebpa-aml.Summary" ref="log$=inpage&link_id=inpage">Summary</a></li><li><a href="#cebpa-aml.Diagnosis" ref="log$=inpage&link_id=inpage">Diagnosis</a></li><li><a href="#cebpa-aml.Clinical_Characteristics" ref="log$=inpage&link_id=inpage">Clinical Characteristics</a></li><li><a href="#cebpa-aml.Genetically_Related_Allelic_Di" ref="log$=inpage&link_id=inpage">Genetically Related (Allelic) Disorders</a></li><li><a href="#cebpa-aml.Differential_Diagnosis" ref="log$=inpage&link_id=inpage">Differential Diagnosis</a></li><li><a href="#cebpa-aml.Management" ref="log$=inpage&link_id=inpage">Management</a></li><li><a href="#cebpa-aml.Genetic_Counseling" ref="log$=inpage&link_id=inpage">Genetic Counseling</a></li><li><a href="#cebpa-aml.Resources" ref="log$=inpage&link_id=inpage">Resources</a></li><li><a href="#cebpa-aml.Molecular_Genetics" ref="log$=inpage&link_id=inpage">Molecular Genetics</a></li><li><a href="#cebpa-aml.Chapter_Notes" ref="log$=inpage&link_id=inpage">Chapter Notes</a></li><li><a href="#cebpa-aml.References" ref="log$=inpage&link_id=inpage">References</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Bulk Download</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="https://ftp.ncbi.nlm.nih.gov/pub/litarch/ca/84/" ref="pagearea=source-links&targetsite=external&targetcat=link&targettype=uri">Bulk download GeneReviews data from FTP</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>GeneReviews Links</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/n/gene/advanced/"><i>GeneReviews</i> Advanced Search</a></li><li><a href="/books/n/gene/glossary/"><i>GeneReviews</i> Glossary</a></li><li><a href="/books/n/gene/resource_mats/">Resource Materials</a> <span class="bk_hlight1">NEW FEATURE</span></li><li><a href="/books/n/gene/updates/">New in <i>GeneReviews</i></a></li><li><a href="/books/n/gene/authors/">Author List</a></li><li><a href="/books/n/gene/prospective_authors/">For Current/Prospective Authors</a></li><li><a href="/books/n/gene/GRpersonnel/"><i>GeneReviews</i> Personnel</a></li><li><a href="/books/n/gene/howto_linkin/">Download/Link to <i>GeneReviews</i></a></li><li><a href="/books/n/gene/contact_us/">Contact Us</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Tests in GTR by Gene</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li>
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</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Variations in ClinVar</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li>
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</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=medgen&DbFrom=books&Cmd=Link&LinkName=books_medgen&IdsFromResult=2346896" ref="log$=recordlinks">MedGen</a><div class="brieflinkpop offscreen_noflow">Related information in MedGen</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=omim&DbFrom=books&Cmd=Link&LinkName=books_omim&IdsFromResult=2346896" ref="log$=recordlinks">OMIM</a><div class="brieflinkpop offscreen_noflow">Related OMIM records</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=2346896" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=2346896" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=gene&DbFrom=books&Cmd=Link&LinkName=books_gene&IdsFromResult=2346896" ref="log$=recordlinks">Gene</a><div class="brieflinkpop offscreen_noflow">Locus Links</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301575" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Fanconi Anemia.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Fanconi Anemia.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Mehta PA, Ebens C. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301372" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Acute Intermittent Porphyria.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Acute Intermittent Porphyria.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Sardh E, Barbaro M. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301625" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Retinoblastoma.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Retinoblastoma.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Lohmann DR, Gallie BL. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301287" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Autoimmune Lymphoproliferative Syndrome.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Autoimmune Lymphoproliferative Syndrome.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Bleesing JJH, Nagaraj CB, Zhang K. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301769" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Diamond-Blackfan Anemia.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Diamond-Blackfan Anemia.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Sieff C. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=20963938" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=20963938" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a href="javascript:historyDisplayState('HTOff')" class="HTOn">Turn Off</a><a href="javascript:historyDisplayState('HTOn')" class="HTOff">Turn On</a></div><ul id="activity"><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67d34345cde49f3df7b78fe9">CEBPA-Associated Familial Acute Myeloid Leukemia (AML) - GeneReviews®</a><div class="ralinkpop offscreen_noflow">CEBPA-Associated Familial Acute Myeloid Leukemia (AML) - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67d34344cde49f3df7b78b19">Table 3. [Notable Familial Acute Myeloid Leukemia-Associated CEBPA Germline Path...</a><div class="ralinkpop offscreen_noflow">Table 3. [Notable Familial Acute Myeloid Leukemia-Associated CEBPA Germline Pathogenic Variants]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67d3434384f3725e59241fa4">Table B. [OMIM Entries for CEBPA-Associated Familial Acute Myeloid Leukemia (AML...</a><div class="ralinkpop offscreen_noflow">Table B. [OMIM Entries for CEBPA-Associated Familial Acute Myeloid Leukemia (AML) (View All in OMIM)]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67d3432ccde49f3df7b70dd3">RecName: Full=CCAAT/enhancer-binding protein alpha; Short=C/EBP alpha</a><div class="ralinkpop offscreen_noflow">RecName: Full=CCAAT/enhancer-binding protein alpha; Short=C/EBP alpha<div class="brieflinkpopdesc">gi|166898082|sp|P49715.3|CEBPA_HUMA</div></div><div class="tertiary">Protein</div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67d3432a67c23b31e09d45e6">Homo sapiens chromosome 19 clone CTD-2540B15, complete sequence</a><div class="ralinkpop offscreen_noflow">Homo sapiens chromosome 19 clone CTD-2540B15, complete sequence<div class="brieflinkpopdesc">gi|28201474|gnl|lanlchgs|2540B15|gb 8738.7|</div></div><div class="tertiary">Nucleotide</div></li></ul><p class="HTOn">Your browsing activity is empty.</p><p class="HTOff">Activity recording is turned off.</p><p id="turnOn" class="HTOff"><a href="javascript:historyDisplayState('HTOn')">Turn recording back on</a></p><a class="seemore" href="/sites/myncbi/recentactivity">See more...</a></div></div></div>
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