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Acute promyelocytic leukemia(APL)

MedGen UID:
44127
Concept ID:
C0023487
Neoplastic Process
Synonym: APL
SNOMED CT: APL - Acute promyelocytic leukemia (110004001); M3 - Acute promyelocytic leukemia (110004001); APML - Acute promyelocytic leukemia (110004001); Acute promyelocytic leukemia, FAB M3 (110004001); Acute promyelocytic leukemia (clinical) (110004001); Acute promyelocytic leukemia (28950004); Acute promyelocytic leukemia with PML::RARA fusion (28950004); Acute promyelocytic leukemia with t(15;17)(q24.1;q21.2) (28950004)
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): RARA (17q21.2)
 
HPO: HP:0004836
Monarch Initiative: MONDO:0012883
OMIM®: 612376
Orphanet: ORPHA520

Definition

Acute promyelocytic leukemia (APL) is associated with 2 cardinal features: a granulocytic differentiation block and reciprocal and balanced translocations that always involve rearrangement of the RARA gene (180240). The most frequent translocation is t(15,17)(q21;q22), which fuses the RARA gene with the PML gene (102578) and represents more than 98% of APL (Vitoux et al., 2007). [from OMIM]

Additional description

From MedlinePlus Genetics
Acute promyelocytic leukemia is a form of acute myeloid leukemia, a cancer of the blood-forming tissue (bone marrow). In normal bone marrow, hematopoietic stem cells produce red blood cells (erythrocytes) that carry oxygen, white blood cells (leukocytes) that protect the body from infection, and platelets (thrombocytes) that are involved in blood clotting. In acute promyelocytic leukemia, immature white blood cells called promyelocytes accumulate in the bone marrow. The overgrowth of promyelocytes leads to a shortage of normal white and red blood cells and platelets in the body, which causes many of the signs and symptoms of the condition.

People with acute promyelocytic leukemia are especially susceptible to developing bruises, small red dots under the skin (petechiae), nosebleeds, bleeding from the gums, blood in the urine (hematuria), or excessive menstrual bleeding. The abnormal bleeding and bruising occur in part because of the low number of platelets in the blood (thrombocytopenia) and also because the cancerous cells release substances that cause excessive bleeding.

The low number of red blood cells (anemia) can cause people with acute promyelocytic leukemia to have pale skin (pallor) or excessive tiredness (fatigue). In addition, affected individuals may heal slowly from injuries or have frequent infections due to the loss of normal white blood cells that fight infection. Furthermore, the leukemic cells can spread to the bones and joints, which may cause pain in those areas. Other general signs and symptoms may occur as well, such as fever, loss of appetite, and weight loss.

Acute promyelocytic leukemia is most often diagnosed around age 40, although it can be diagnosed at any age.  https://medlineplus.gov/genetics/condition/acute-promyelocytic-leukemia

Clinical features

From HPO
Acute promyelocytic leukemia
MedGen UID:
44127
Concept ID:
C0023487
Neoplastic Process
Acute promyelocytic leukemia (APL) is associated with 2 cardinal features: a granulocytic differentiation block and reciprocal and balanced translocations that always involve rearrangement of the RARA gene (180240). The most frequent translocation is t(15,17)(q21;q22), which fuses the RARA gene with the PML gene (102578) and represents more than 98% of APL (Vitoux et al., 2007).
Abnormal granulocytopoietic cell morphology
MedGen UID:
868631
Concept ID:
C4023031
Finding
An anomaly of cells involved in the formation of a granulocytes, that is, of the granulocytopoietic cell.

Conditions with this feature

Acute promyelocytic leukemia
MedGen UID:
44127
Concept ID:
C0023487
Neoplastic Process
Acute promyelocytic leukemia (APL) is associated with 2 cardinal features: a granulocytic differentiation block and reciprocal and balanced translocations that always involve rearrangement of the RARA gene (180240). The most frequent translocation is t(15,17)(q21;q22), which fuses the RARA gene with the PML gene (102578) and represents more than 98% of APL (Vitoux et al., 2007).

Professional guidelines

PubMed

Kantarjian HM, DiNardo CD, Kadia TM, Daver NG, Altman JK, Stein EM, Jabbour E, Schiffer CA, Lang A, Ravandi F
CA Cancer J Clin 2025 Jan-Feb;75(1):46-67. Epub 2024 Dec 10 doi: 10.3322/caac.21873. PMID: 39656142Free PMC Article
Yilmaz M, Kantarjian H, Ravandi F
Blood Cancer J 2021 Jun 30;11(6):123. doi: 10.1038/s41408-021-00514-3. PMID: 34193815Free PMC Article
Sanz MA, Fenaux P, Tallman MS, Estey EH, Löwenberg B, Naoe T, Lengfelder E, Döhner H, Burnett AK, Chen SJ, Mathews V, Iland H, Rego E, Kantarjian H, Adès L, Avvisati G, Montesinos P, Platzbecker U, Ravandi F, Russell NH, Lo-Coco F
Blood 2019 Apr 11;133(15):1630-1643. Epub 2019 Feb 25 doi: 10.1182/blood-2019-01-894980. PMID: 30803991Free PMC Article

Curated

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Myeloid Leukemia, 2023

DailyMed Drug Label, TRISENOX, 2021

Recent clinical studies

Etiology

Salhotra A, Mei M
Cancer Treat Res 2021;181:45-55. doi: 10.1007/978-3-030-78311-2_3. PMID: 34626354
Iland HJ
Semin Hematol 2019 Apr;56(2):131-138. Epub 2018 Aug 23 doi: 10.1053/j.seminhematol.2018.07.004. PMID: 30926089
Lo-Coco F, Cicconi L
Curr Hematol Malig Rep 2014 Jun;9(2):138-43. doi: 10.1007/s11899-014-0206-5. PMID: 24729066
Baljevic M, Park JH, Stein E, Douer D, Altman JK, Tallman MS
Hematol Oncol Clin North Am 2011 Dec;25(6):1215-33, viii. doi: 10.1016/j.hoc.2011.10.002. PMID: 22093584Free PMC Article
Ganser A, Hoelzer D
Curr Opin Hematol 1994 Jul;1(4):248-55. PMID: 9371290

Diagnosis

Fujita H
Int J Hematol 2024 May;119(5):481-492. Epub 2024 Apr 17 doi: 10.1007/s12185-024-03749-5. PMID: 38630356
Malaga ML, Carrillo LF
Blood 2023 Oct 12;142(15):1328. doi: 10.1182/blood.2023021869. PMID: 37824159
Fang H, Wang SA, Hu S, Konoplev SN, Mo H, Liu W, Zuo Z, Xu J, Jorgensen JL, Yin CC, El Hussein S, Jelloul FZ, Tang Z, Medeiros LJ, Wang W
Cytometry B Clin Cytom 2022 Jul;102(4):283-291. Epub 2022 Jun 18 doi: 10.1002/cyto.b.22085. PMID: 35716019
Salhotra A, Mei M
Cancer Treat Res 2021;181:45-55. doi: 10.1007/978-3-030-78311-2_3. PMID: 34626354
Yilmaz M, Kantarjian H, Ravandi F
Blood Cancer J 2021 Jun 30;11(6):123. doi: 10.1038/s41408-021-00514-3. PMID: 34193815Free PMC Article

Therapy

Fujita H
Int J Hematol 2024 May;119(5):481-492. Epub 2024 Apr 17 doi: 10.1007/s12185-024-03749-5. PMID: 38630356
Stein EM, Tallman MS
Acta Haematol 2014;132(3-4):307-12. Epub 2014 Sep 10 doi: 10.1159/000365117. PMID: 25228556
Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia
N Engl J Med 2013 Jul 11;369(2):111-21. doi: 10.1056/NEJMoa1300874. PMID: 23841729
Litzow MR
Expert Opin Pharmacother 2008 Jul;9(10):1773-85. doi: 10.1517/14656566.9.10.1773. PMID: 18570609
Aquino VM
Curr Probl Pediatr Adolesc Health Care 2002 Feb;32(2):50-8. doi: 10.1067/mps.2002.121791. PMID: 11951090

Prognosis

Kantarjian HM, Kadia TM, DiNardo CD, Welch MA, Ravandi F
Cancer 2021 Apr 15;127(8):1186-1207. Epub 2021 Mar 18 doi: 10.1002/cncr.33477. PMID: 33734442
Helbig G, Koclęga A, Liwoch R, Wiśniewski-Piąty K, Bober G
Pol Arch Intern Med 2017 Jun 30;127(6):448-449. Epub 2017 Jun 29 doi: 10.20452/pamw.4052. PMID: 28680029
Abedin S, Altman JK
Hematology Am Soc Hematol Educ Program 2016 Dec 2;2016(1):10-15. doi: 10.1182/asheducation-2016.1.10. PMID: 27913456Free PMC Article
Stein EM, Tallman MS
Acta Haematol 2014;132(3-4):307-12. Epub 2014 Sep 10 doi: 10.1159/000365117. PMID: 25228556
Deschler B, Lübbert M
Cancer 2006 Nov 1;107(9):2099-107. doi: 10.1002/cncr.22233. PMID: 17019734

Clinical prediction guides

Zhang Y, Lou J, Liu Y, Jin P, Tan Y, Song H, Jin W, Wang D, Dong F, Wu S, Fang H, Chen S, Chen Z, Wang K
Proc Natl Acad Sci U S A 2024 Aug 20;121(34):e2406519121. Epub 2024 Aug 13 doi: 10.1073/pnas.2406519121. PMID: 39136995Free PMC Article
Jin W, Dai Y, Chen L, Zhu H, Dong F, Zhu H, Meng G, Li J, Chen S, Chen Z, Fang H, Wang K
Nat Commun 2024 Feb 16;15(1):1423. doi: 10.1038/s41467-024-45737-7. PMID: 38365836Free PMC Article
Ten Cate H, Leader A
Hamostaseologie 2021 Apr;41(2):120-126. Epub 2021 Apr 15 doi: 10.1055/a-1393-8302. PMID: 33860520
Gurnari C, Breccia M, Di Giuliano F, Scalzulli E, Divona M, Piciocchi A, Cicconi L, De Bellis E, Venditti A, Del Principe MI, Arcese W, Lo-Coco F, Garaci F, Voso MT
Br J Haematol 2021 Apr;193(1):129-132. Epub 2020 Aug 10 doi: 10.1111/bjh.17018. PMID: 32808672
Huang J, Sun M, Wang Z, Zhang Q, Lou J, Cai Y, Chen W, Du X
Oncotarget 2016 Nov 1;7(44):71974-71986. doi: 10.18632/oncotarget.12451. PMID: 27713127Free PMC Article

Recent systematic reviews

Bønløkke ST, Ommen HB, Hvas AM
Semin Thromb Hemost 2021 Jul;47(5):569-580. Epub 2021 May 31 doi: 10.1055/s-0041-1725099. PMID: 34058766
Ahrari A, Al-Ani F, Wang YP, Lazo-Langner A
Thromb Res 2019 Jun;178:1-6. Epub 2019 Mar 20 doi: 10.1016/j.thromres.2019.03.014. PMID: 30921533
Verma V, Giri S, Manandhar S, Pathak R, Bhatt VR
Leuk Lymphoma 2016;57(3):616-22. Epub 2015 Jul 28 doi: 10.3109/10428194.2015.1065977. PMID: 26110880
Martí-Carvajal AJ, Anand V, Solà I
Cochrane Database Syst Rev 2015 Jun 24;2015(6):CD008562. doi: 10.1002/14651858.CD008562.pub3. PMID: 26107113Free PMC Article
Rashidi A, Fisher SI
Med Oncol 2013;30(3):625. Epub 2013 Jun 15 doi: 10.1007/s12032-013-0625-5. PMID: 23771799

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