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<meta name="description" content="hnRNP K regulates cellular programs, and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knockout allele (Hnrnpk(+/-)). Hnrnpk haploinsufficiency resulted in …"><meta name="keywords" content="pmid:26412324, PMC4652598, doi:10.1016/j.ccell.2015.09.001, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Miguel Gallardo, Hun Ju Lee, Sean M Post, Animals, Cell Differentiation, Cell Proliferation, Cells, Cultured, Chromosomal Instability, Chromosomes, Human, Pair 9 / genetics, Gene Expression Regulation, Neoplastic, Gene Knockout Techniques, Haploinsufficiency*, Hematologic Neoplasms / genetics, Hematologic Neoplasms / metabolism, Hematologic Neoplasms / pathology*, Heterogeneous-Nuclear Ribonucleoprotein K, Humans, Mice, Ribonucleoproteins / genetics*, Ribonucleoproteins / metabolism*, Signal Transduction, Survival Analysis, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/26412324/"><meta property="og:description" content="hnRNP K regulates cellular programs, and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knockout allele (Hnrnpk(+/-)). Hnrnpk haploinsufficiency resulted in …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/26412324/"><meta name="twitter:description" content="hnRNP K regulates cellular programs, and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knockout allele (Hnrnpk(+/-)). Hnrnpk haploinsufficiency resulted in …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">
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||
data-ga-category="featured_link"
|
||
data-ga-action="clipboard">
|
||
Clipboard <span class="amount-in-clipboard"></span>
|
||
</a>
|
||
</div>
|
||
|
||
<span class="search-input-link user-guide-link" role="navigation" aria-label="User guide">
|
||
<a href="/help/"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F26412324%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F26412324%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sq4bPvxzeARp0l2yvyIxtTtaHVzqrDStJdOgsl0VObETUM8o8RlzX1ZOfZhCkeqN">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sq4bPvxzeARp0l2yvyIxtTtaHVzqrDStJdOgsl0VObETUM8o8RlzX1ZOfZhCkeqN">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sq4bPvxzeARp0l2yvyIxtTtaHVzqrDStJdOgsl0VObETUM8o8RlzX1ZOfZhCkeqN">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 26412324 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 26412324"/>
|
||
<input type="hidden" name="email-subject-hash" value="b4d339deec100b0c116eb5efae3799370ce83b7c82fb72b9eee2e51dee40b173"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sq4bPvxzeARp0l2yvyIxtTtaHVzqrDStJdOgsl0VObETUM8o8RlzX1ZOfZhCkeqN">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sq4bPvxzeARp0l2yvyIxtTtaHVzqrDStJdOgsl0VObETUM8o8RlzX1ZOfZhCkeqN">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sq4bPvxzeARp0l2yvyIxtTtaHVzqrDStJdOgsl0VObETUM8o8RlzX1ZOfZhCkeqN">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sq4bPvxzeARp0l2yvyIxtTtaHVzqrDStJdOgsl0VObETUM8o8RlzX1ZOfZhCkeqN">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sq4bPvxzeARp0l2yvyIxtTtaHVzqrDStJdOgsl0VObETUM8o8RlzX1ZOfZhCkeqN">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="26412324">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://linkinghub.elsevier.com/retrieve/pii/S1535-6108(15)00305-0"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=26412324&db=pubmed&nlmid=101130617"
|
||
title="See full text options at Elsevier Science"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Elsevier Science"
|
||
data-ga-label="26412324"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-celloa.png" alt="Elsevier Science full text link"><span class="text">
|
||
|
||
Elsevier Science
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/26412324/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=26412324&db=pubmed&nlmid=101130617"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="26412324"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/26412324/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/26412324/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="26412324" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F26412324%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="sq4bPvxzeARp0l2yvyIxtTtaHVzqrDStJdOgsl0VObETUM8o8RlzX1ZOfZhCkeqN"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region"><button
|
||
class="trigger usa-button"
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</a></li></ul></div></div></div><span class="period">. </span><span class="cit">2015 Oct 12;28(4):486-499.</span>
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<h1 class="heading-title">
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hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies
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hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies
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<p>
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hnRNP K regulates cellular programs, and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knockout allele (Hnrnpk(+/-)). Hnrnpk haploinsufficiency resulted in reduced survival, increased tumor formation, genomic instability, and the development of transplantable hematopoietic neoplasms with myeloproliferation. Reduced hnRNP K expression attenuated p21 activation, downregulated C/EBP levels, and activated STAT3 signaling. Additionally, analysis of samples from primary acute myeloid leukemia patients harboring a partial deletion of chromosome 9 revealed a significant decrease in HNRNPK expression. Together, these data implicate hnRNP K in the development of hematological disorders and suggest hnRNP K acts as a tumor suppressor.
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Copyright © 2015 Elsevier Inc. All rights reserved.
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Conflict of interest statement
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one"><bold>Conflicts of interests:</bold> The authors declare no conflicts.</p>
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Figures
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<strong class="figure-label">
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<p> Figure 1. <i> HNRNPK </i> expression is reduced in… </p>
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<p> Figure 1. <i> HNRNPK </i> expression is reduced in patients with AML that harbor a 9q deletion </p>
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Figure 1. <i>HNRNPK</i> expression is reduced in patients with AML that harbor a 9q deletion
|
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||
<div class="figure-caption-contents">Quantitative RT-PCR analysis of <i>HNRNPK</i> levels from bone marrow aspirates of AML patients who carry 9q deletions (n = 12) and healthy donors controls (n = 8) (p = 0.0001). Data are represented as mean ± SEM determined from triplicate samples after normalization to geometric mean of β-ACTIN and <i>GAPDH.</i> ***p < 0.005. P-values were calculated using the Mann-Whitney test.</div>
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<p> Figure 2. Generation of <i> Hnrnpk </i> haploinsufficient mice </p>
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<p> Figure 2. Generation of <i> Hnrnpk </i> haploinsufficient mice </p>
|
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|
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<div class="figure-caption-contents"><p> (A) Schema of the <i> Hnrnpk </i> locus and the… </p></div>
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Figure 2. Generation of <i>Hnrnpk</i> haploinsufficient mice
|
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|
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<div class="figure-caption-contents">(A) Schema of the <i>Hnrnpk</i> locus and the KOMP targeting vector (<i>Hnrnpk<sup>1(KOMP)Wtsi</sup></i>). The targeting vector replaced exons 3 through 6 and with a neomycin selectable marker flanked by <i>LoxP</i> sites (ovals) and LacZ cassette flanked by <i>Flp</i> sites (arrowheads). Black numbered boxes denote <i>Hnrnpk</i> exons. (B) PCR analysis of targeted recombination in <i>Hnrnpk<sup>+/−</sup></i> mice. The 5.9-kb amplicon (dark blue arrow heads) represents the recombined <i>Hnrnpk</i> allele using external and internal primers for the 5′ arm. Wild-type DNA serves as a negative control. The 10.1-kb (black arrow heads), 9.1-kb (red arrow heads), 8.1-kb (green arrow heads), and 5.5-kb (light blue arrow heads) amplicons represent the recombined <i>Hnrnpk</i> allele using external and internal primers for the 3′ arm. See also: Figure S1.</div>
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data-figure-id="F3">
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<img class="figure-thumb" itemprop="thumbnail"
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id="article-image-2"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e9/4652598/3ce37e1efeee/nihms734287f3.gif"
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alt="Figure 3" />
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<strong class="figure-label">
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<p> Figure 3. <i> Hnrnpk <sup> +/− </sup> </i> mice have developmental… </p>
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</strong>
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<strong class="figure-label">
|
||
<p> Figure 3. <i> Hnrnpk <sup> +/− </sup> </i> mice have developmental defects and reduced hnRNP K expression </p>
|
||
</strong>
|
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<div class="figure-caption-contents"><p> (A) Observed and… </p></div>
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<strong class="figure-label">
|
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Figure 3. <i>Hnrnpk<sup>+/−</sup></i> mice have developmental defects and reduced hnRNP K expression
|
||
</strong>
|
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||
<div class="figure-caption-contents">(A) Observed and expected number of <i>Hnrnpk<sup>+/−</sup></i> and wild type mice at weaning (21 days). (B) Growth retardation in <i>Hnrnpk<sup>+/−</sup></i> mice at day 3 (Left panel) and 10 days (Right panel). (C) Weight (in grams) of <i>Hnrnpk<sup>+/−</sup></i> (n = 10) and wild type littermates (n = 8) over the first four weeks of life (p = 0.0001). (D) Weight analysis (in grams) of adult <i>Hnrnpk<sup>+/−</sup></i> and wild type mice stratified by sex (Female, p = 0.011) and (Male, p = 0.003). (E) Observed and expected ratio of <i>Hnrnpk</i>−/−, <i>Hnrnpk<sup>+/−</sup></i>, and wild type mice from 12 separate <i>hnRNP K</i><sup>+/−</sup> matings at weaning (21 days). (F) Quantitative RT-PCR analysis of <i>Hnrnpk</i> expression in the bone marrow of wild type (n = 4) and <i>Hnrnpk<sup>+/−</sup></i> (n = 4) mice (p = 0.0396). (G) Western blot analyses of hnRNP K levels in lysates from wild type and <i>Hnrnpk<sup>+/−</sup></i> mice, (upper-left panel: MEFs; upper-right panel: whole bone marrow; bottom-left panel: spleen; bottom-right panel: liver). Data are represented as mean ± SEM. *p < 0.05 and ***p < 0.005. p-values were calculated using Mann-Whitney test.</div>
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data-label-slug="figure-4">
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<a class="figure-link"
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e9/4652598/8cb98934a4eb/nihms734287f4.jpg"
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data-image-width="750"
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data-image-alt="Figure 4"
|
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data-pmc-id="PMC4652598"
|
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data-figure-id="F4">
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<img class="figure-thumb" itemprop="thumbnail"
|
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id="article-image-3"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e9/4652598/28e4474af5ec/nihms734287f4.gif"
|
||
alt="Figure 4" />
|
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</a>
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<strong class="figure-label">
|
||
<p> Figure 4. Reduced hnRNP K expression results… </p>
|
||
</strong>
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<strong class="figure-label">
|
||
<p> Figure 4. Reduced hnRNP K expression results in increased proliferation and a dampened p21 response… </p>
|
||
</strong>
|
||
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<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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|
||
<strong class="figure-label">
|
||
Figure 4. Reduced hnRNP K expression results in increased proliferation and a dampened p21 response following DNA damage
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">(A) Increased cell proliferation in <i>Hnrnpk<sup>+/−</sup></i> MEFs. Three low passage (P2) MEF cell lines per genotype were plated for 24, 48 or 72 hr, and then assayed by WST-8 (p = 0.0070). Each data point represents the mean ± SEM for three separate MEF lines per genotype (B) Quantitative RT-PCR analysis of <i>p21</i> levels before and after irradiation from WT and <i>Hnrnpk<sup>+/−</sup></i> MEFs. (C) Western blot analysis of hnRNP K and p21 expression in lysates from γ-IR treated wild type and <i>Hnrnpk<sup>+/−</sup></i> MEFs. β-actin serves as an internal control. Data are represented as mean ± SEM. ***p < 0.005. P-values were calculated using unpaired t-tests and Mann-Whitney tests. See also, Figure S2.</div>
|
||
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||
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||
</figcaption>
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data-label-slug="figure-5">
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<a class="figure-link"
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e9/4652598/f2b5294e6372/nihms734287f5.jpg"
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data-image-width="750"
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data-image-height="677"
|
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data-image-alt="Figure 5"
|
||
data-pmc-id="PMC4652598"
|
||
data-figure-id="F5">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
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id="article-image-4"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e9/4652598/55ce2d30e032/nihms734287f5.gif"
|
||
alt="Figure 5" />
|
||
</a>
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|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 5. <i> Hnrnpk <sup> +/− </sup> </i> mice develop myeloid… </p>
|
||
</strong>
|
||
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||
|
||
|
||
|
||
|
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|
||
</div>
|
||
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|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 5. <i> Hnrnpk <sup> +/− </sup> </i> mice develop myeloid hyperplasia </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> (A) Cell blood count (CBC) of peripheral blood… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Figure 5. <i>Hnrnpk<sup>+/−</sup></i> mice develop myeloid hyperplasia
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">(A) Cell blood count (CBC) of peripheral blood comparing neutrophils (p = 0.0006) and basophils (p = 0.0477) from wild type (n = 8) and <i>Hnrnpk<sup>+/−</sup></i> (n = 11) mice and platelets (p = 0.0095) of wild type (n = 6) and <i>hnRNP K</i><sup>+/−</sup> (n = 6) mice. (B) Flow cytometry analysis of double positive Ly6G/CD11b myeloid populations (50,000 gated cells) in the peripheral blood of wild type (n = 6) and <i>hnRNP K</i><sup>+/−</sup> (n =6) (upper panel, p = 0.0354) and bone marrow of wild type (n = 7) and <i>hnRNP K</i><sup>+/−</sup> (n = 13) (bottom panel, p = 0.0008) mice. Percentages were compared and analyzed using Mann-Whitney test. Data are represented as mean ± SEM. *p < 0.05, **p < 0.01, and ***p < 0.005. See also, Figure S3.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
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data-label-slug="figure-6">
|
||
<a class="figure-link"
|
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e9/4652598/a847906c1bfe/nihms734287f6.jpg"
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|
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data-image-alt="Figure 6"
|
||
data-pmc-id="PMC4652598"
|
||
data-figure-id="F6">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
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id="article-image-5"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e9/4652598/97dd08588c03/nihms734287f6.gif"
|
||
alt="Figure 6" />
|
||
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|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 6. <i> Hnrnpk <sup> +/− </sup> </i> mice have reduced… </p>
|
||
</strong>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
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|
||
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|
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|
||
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||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 6. <i> Hnrnpk <sup> +/− </sup> </i> mice have reduced survival and are tumor prone </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> (A) Kaplan-Meier curves indicating… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
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||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Figure 6. <i>Hnrnpk<sup>+/−</sup></i> mice have reduced survival and are tumor prone
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">(A) Kaplan-Meier curves indicating survival of <i>Hnrnpk<sup>+/−</sup></i> (n = 76) and wild type (n = 37) mice. Statistical significance was determined by log rank test (p = 0.0001). (B) <i>Hnrnpk</i> haploinsufficiency results in tumor phenotypes (n = 55; 62% myeloproliferation, 31% lymphoma and 4% hepatocellular carcinoma). (C) Hematoxylin and Eosin (H&E) staining of paraffin-embedded bone marrow sections and peripheral blood (PB) smears from wild type <i>Hnrnpk<sup>+/−</sup></i> mice diagnosed with myeloid hyperplasias. The scale bar for H&E staining represents 50 μm and 25 μm for PB smears. (D) H&E staining of paraffin-embedded splenic sections and PB smears from wild type and lymphoma burdened <i>Hnrnpk<sup>+/−</sup></i> mice. (E) H&E and immunohistochemical staining of malignant T-cell (CD3 positive, Bottom Panel) and B-cell (B220 positive, Top Panel) lymphomas in the liver of <i>Hnrnpk<sup>+/−</sup></i> mice. (F) H&E staining of paraffin-embedded liver sections from wild type and <i>Hnrnpk<sup>+/−</sup></i> mice diagnosed with hepatocellular carcinoma. See also Figure S4.</div>
|
||
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||
|
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||
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||
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|
||
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||
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||
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|
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|
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<a class="figure-link"
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e9/4652598/64020fb86f7d/nihms734287f7.jpg"
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data-image-alt="Figure 7"
|
||
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|
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data-figure-id="F7">
|
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<img class="figure-thumb" itemprop="thumbnail"
|
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id="article-image-6"
|
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e9/4652598/cb2e114c7a73/nihms734287f7.gif"
|
||
alt="Figure 7" />
|
||
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|
||
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|
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<strong class="figure-label">
|
||
<p> Figure 7. hnRNP K-mediated activation of cytokines… </p>
|
||
</strong>
|
||
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||
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|
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|
||
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||
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||
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||
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||
|
||
<strong class="figure-label">
|
||
<p> Figure 7. hnRNP K-mediated activation of cytokines contributes to proliferation and differentiation phenotypes </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> (A) Cytokines… </p></div>
|
||
|
||
|
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|
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|
||
</div>
|
||
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||
<figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
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|
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|
||
|
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|
||
<strong class="figure-label">
|
||
Figure 7. hnRNP K-mediated activation of cytokines contributes to proliferation and differentiation phenotypes
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">(A) Cytokines array analysis of IL-3, IL-6, G-CSF and GM-CSF levels in the peripheral blood of wild type (n = 10) and <i>Hnrnpk<sup>+/−</sup></i> mice (n = 9) diagnosed with myeloid hyperplasia (IL-3: p = 0.0002, IL-6: p = 0.0004, G-CSF: p = 0.0002, and GM-CSF: p = 0.0002). (B) Analyses of colony formation assays after 14 days using Lin-CD117+ hematopoietic stem cells from wild type (n = 8) and <i>Hnrnpk<sup>+/−</sup></i> (n = 17) mice (number of colonies: p = 0.0078 and number of cells: p = 0.0001). All experiments were performed in triplicate. Data are represented as mean ± SEM. **p < 0.01 and ***p < 0.005. P-values were calculated using Mann-Whitney test. (C) Replating analysis of Lin-CD117+ hematopoietic stem cells from wild type (n = 5) and <i>Hnrnpk<sup>+/−</sup></i> (n = 7) mice. Each passage was analyzed every 14 days. All experiments were performed in quadruplicate. Data are represented as mean ± SEM. (D) Flow cytometry analysis of CD45.1+ (host) and CD45.2+ (donor) in the transplanted host mice and B220+ and Ly6G+ cells within the CD45.2+ population. (E) CBC analysis of untransplanted NSG (control) mice and NSG mice transplanted with wild type or <i>Hnrnpk<sup>+/−</sup></i> HSCs. (F) Wright's staining of peripheral blood (PB) smears from NSG mice transplanted with wild type or <i>Hnrnpk<sup>+/−</sup></i> HSCs harboring malignant lymphoid cells. See also, Figure S5.</div>
|
||
|
||
|
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||
|
||
</figcaption>
|
||
|
||
|
||
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|
||
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|
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|
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|
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|
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|
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|
||
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|
||
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|
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<img class="figure-thumb" itemprop="thumbnail"
|
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|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e9/4652598/476ace34077a/nihms734287f8.gif"
|
||
alt="Figure 8" />
|
||
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|
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|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 8. <i> Hnrnpk </i> haploinsufficiency alters expression of… </p>
|
||
</strong>
|
||
|
||
|
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|
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|
||
|
||
|
||
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|
||
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|
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|
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
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|
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|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 8. <i> Hnrnpk </i> haploinsufficiency alters expression of genes controlling proliferation and differentiation </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> (A) Western blot… </p></div>
|
||
|
||
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<strong class="figure-label">
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Figure 8. <i>Hnrnpk</i> haploinsufficiency alters expression of genes controlling proliferation and differentiation
|
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</strong>
|
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<div class="figure-caption-contents">(A) Western blot analysis of C/EBPα and C/EBPβ from lysates of wild type and <i>Hnrnpk<sup>+/−</sup></i> mice. Upper arrow denotes the p42 isoform of C/EBPα and the lower arrow marks the p30 isoform. β-actin serves as a loading control. (B) Quantitative RT-PCR analysis of <i>C/EBPα</i> and <i>C/EBPβ</i> levels from whole bone marrows of wild type (n = 8) and <i>Hnrnpk<sup>+/−</sup></i> (n = 10) mice <i>(C/EBPα:</i> p = 0.042 and <i>C/EBPβ:</i> p = 0.020). (C) Quantitative RT-PCR analysis <i>of p21</i> levels in wild type (n = 8) and <i>Hnrnpk<sup>+/−</sup></i> (n = 10) bone marrows (p = 0.0044). (D) Immunohistochemical analysis of phos-Y705Stat3 levels in the bone marrow wild type and <i>Hnrnpk<sup>+/−</sup></i> mice diagnosed with myeloid hyperplasia. The scale bar represents 50 μm. (E) ChIP analysis of hnRNP K interacting with the <i>C/EBPα, C/EBPβ</i> and <i>p21</i> genes in wild type or <i>Hnrnpk<sup>+/−</sup></i> tissues. Each rectangle represents the corresponding gene. The closed black box denoted the region harboring a putative hnRNP K binding sequence that is amplified by the corresponding primer sets. The “check-mark” denotes positive hnRNP K binding and the “X” denotes a lack of interaction. (F) Quantitative RT-PCR analysis of <i>TNFα</i> levels in spleens from wild type (n = 7) and tumor burdened <i>Hnrnpk<sup>+/−</sup></i> (n = 5) mice (p = 0.0177). (G) H&E staining and immunohistochemical analyses of B220, TNF<i>α</i>, and phos-Y705STAT3 expression in <i>Hnrnpk<sup>+/−</sup></i> mice with malignant lymphoid infiltration in the liver. Data are represented as mean ± SEM. *p < 0.05 and ***p < 0.005. P-values were calculated using unpaired t and Mann-Whitney tests. See also Figure S6.</div>
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<span class="docsum-authors full-authors">Dvinge H, Kim E, Abdel-Wahab O, Bradley RK.</span>
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<span class="docsum-authors short-authors">Dvinge H, et al.</span>
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<span class="docsum-journal-citation full-journal-citation">Nat Rev Cancer. 2016 Jul;16(7):413-30. doi: 10.1038/nrc.2016.51. Epub 2016 Jun 10.</span>
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<span class="docsum-authors full-authors">Alanazi B, Munje CR, Rastogi N, Williamson AJK, Taylor S, Hole PS, Hodges M, Doyle M, Baker S, Gilkes AF, Knapper S, Pierce A, Whetton AD, Darley RL, Tonks A.</span>
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<span class="docsum-authors short-authors">Alanazi B, et al.</span>
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<span class="docsum-journal-citation full-journal-citation">Leukemia. 2020 Feb;34(2):427-440. doi: 10.1038/s41375-019-0596-4. Epub 2019 Oct 14.</span>
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Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368:2059–2074.
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Bochkis IM, Rubins NE, White P, Furth EE, Friedman JR, Kaestner KH. Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress. Nat Med. 2008;14:828–836.
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Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol. 2011;29:487–494.
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Dayyani F, Wang J, Yeh JR, Ahn EY, Tobey E, Zhang DE, Bernstein ID, Peterson RT, Sweetser DA. Loss of TLE1 and TLE4 from the del(9q) commonly deleted region in AML cooperates with AML1-ETO to affect myeloid cell proliferation and survival. Blood. 2008;111:4338–4347.
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Enge M, Bao W, Hedstrom E, Jackson SP, Moumen A, Selivanova G. MDM2-dependent downregulation of p21 and hnRNP K provides a switch between apoptosis and growth arrest induced by pharmacologically activated p53. Cancer Cell. 2009;15:171–183.
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aria-expanded="false"
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data-pinger-ignore>
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Cell Proliferation
|
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</button><div id="keyword-actions-mesh-terms-2"
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class="keyword-actions-dropdown dropdown dropdown-container"
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aria-label="Dropdown menu for keyword Cell Proliferation"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Cell+Proliferation%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Cell+Proliferation%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Cell Proliferation"[MeSH]"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Cells, Cultured
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aria-label="Dropdown menu for keyword Cells, Cultured"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Chromosomal Instability
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Chromosomes, Human, Pair 9 / genetics
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Gene Expression Regulation, Neoplastic
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Search in PubMed
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Search in MeSH
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Gene Knockout Techniques
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|
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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aria-label="Toggle dropdown menu for keyword Haploinsufficiency*"
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tabindex="0"
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aria-expanded="false"
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|
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Haploinsufficiency*
|
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</button><div id="keyword-actions-mesh-terms-major-8"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Haploinsufficiency*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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data-href="/?term=%22Haploinsufficiency%22%5BMAJR%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Haploinsufficiency"[MAJR]"
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Search in PubMed
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Hematologic Neoplasms / genetics"
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
|
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Hematologic Neoplasms / genetics
|
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</button><div id="keyword-actions-mesh-terms-9"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Hematologic Neoplasms / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Hematologic+Neoplasms%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Hematologic+Neoplasms%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Hematologic Neoplasms/genetics"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Hematologic+Neoplasms"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-ga-category="search"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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tabindex="0"
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aria-expanded="false"
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|
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Hematologic Neoplasms / metabolism
|
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</button><div id="keyword-actions-mesh-terms-10"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Hematologic Neoplasms / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Hematologic+Neoplasms%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Hematologic+Neoplasms%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Hematologic Neoplasms/metabolism"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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aria-label="Toggle dropdown menu for keyword Hematologic Neoplasms / pathology*"
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tabindex="0"
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aria-expanded="false"
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|
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Hematologic Neoplasms / pathology*
|
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</button><div id="keyword-actions-mesh-terms-major-11"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Hematologic Neoplasms / pathology*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Hematologic+Neoplasms%2Fpathology%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Hematologic+Neoplasms%2Fpathology%22%5BMAJR%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Hematologic Neoplasms/pathology"[MAJR]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Heterogeneous-Nuclear Ribonucleoprotein K"
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aria-expanded="false"
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data-pinger-ignore>
|
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Heterogeneous-Nuclear Ribonucleoprotein K
|
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</button><div id="keyword-actions-mesh-terms-12"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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|
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<div id="substances" class="substances keywords-section">
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<h2 class="title">
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Substances
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</h2>
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<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Heterogeneous-Nuclear Ribonucleoprotein K
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Ribonucleoproteins
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aria-label="Dropdown menu for keyword Ribonucleoproteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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HNRNPK protein, human
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