<table><tbody><tr><td><table cellpadding="2" cellspacing="0" width="600"><tbody><tr bgcolor="#cccccc" valign="top"><td colspan="2"><table width="600"><tbody><tr><td><strong class="acc" id="GSE283119"><a href="/geo/query/acc.cgi?acc=GSE283119" onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_recenter)">Series GSE283119</a></strong></td>

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<td align="right" onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_gds)"><a href="/gds/?term=GSE283119[Accession]">Query DataSets for GSE283119</a></td>

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<tr valign="top"><td>Status</td>

<td>Public on Apr 09, 2025</td>

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<tr valign="top"><td nowrap="">Title</td>

<td style="text-align: justify">Linker histone H1-0 is a specific mediator of the ETV6::RUNX1 transcriptional landscape in preleukemia and B cell acute lymphoblastic leukemia</td>

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<tr valign="top"><td nowrap="">Organism</td>

<td><a href="/Taxonomy/Browser/wwwtax.cgi?mode=Info&amp;id=9606" onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_organismus)">Homo sapiens</a></td>

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<tr valign="top"><td nowrap="">Experiment type</td>

<td>Expression profiling by high throughput sequencing<br></td>

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<tr valign="top"><td nowrap="">Summary</td>

<td style="text-align: justify">The chimeric hematopoietic transcription factor ETV6::RUNX1 is the most common oncogenic fusion in pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL). It induces a clinically silent preleukemic state that requires secondary mutations for progression to full-blown leukemia. ETV6::RUNX1 functions primarily through repression of RUNX1 binding sites. In order to elucidate the characteristic quiescent state of ETV6::RUNX1 expressing cells, we generated preleukemic human induced pluripotent stem cell (hiPSC) models from two healthy donors using CRISPR/Cas9 gene editing. We identified upregulation of linker histone H1-0 in preleukemic hiPSCs, which was preserved upon hematopoietic differentiation and transformation to overt BCP-ALL. ETV6::RUNX1 induces activity of the H1-0 promoter whereas depletion of H1-0 specifically inhibited ETV6::RUNX1 signature genes, indicating its role as a novel key mediator of the quiescent ETV6::RUNX1 transcriptional profile. Single-cell gene expression analysis revealed that H1-0 levels strongly anti-correlate with cellular transcriptional activity, resulting in particularly high expression in quiescent cells during hematopoietic development. Pharmacologically, H1-0 protein levels correspond to susceptibility of BCP-ALL towards histone deacetylase inhibitor (HDACi) treatment and our data indicate efficacy of combinatorial drug treatment using the potent H1-0-inducing HDACi Quisinostat in BCP-ALL expressing high basal H1-0 levels.<br></td>

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<tr valign="top"><td nowrap="">&nbsp;</td>

<td></td>

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<tr valign="top"><td nowrap="">Overall design</td>

<td style="text-align: justify">To analyze transcriptional changes induced by HDACi treatment, BCP-ALL cell lines were treated with 1 µM Quisinostat or DMSO for 24 hours.<br></td>

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<tr valign="top"><td nowrap="">&nbsp;</td>

<td></td>

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<tr valign="top"><td>Contributor(s)</td>

<td><a href="/pubmed/?term=Vera Helena J[Author]">Vera Helena J</a>, <a href="/pubmed/?term=Ute F[Author]">Ute F</a></td>

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<tr valign="top"><td nowrap="">Citation(s)</td>

<td><span class="pubmed_id" id="40177616"><!--?xml version="1.0" encoding="UTF-8"?-->

<div class="PubmedCitation"><ul><li><span class="authors">Jepsen VH, Hanel A, Picard D, Bhave R et al. </span><span class="title">H1-0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape in preleukemia and B cell acute lymphoblastic leukemia. </span><span class="source">Hemasphere</span> 2025 Apr;9(4):e70116. PMID:&nbsp;<a title="Link to PubMed record" href="https://www.ncbi.nlm.nih.gov/pubmed/40177616">40177616</a></li></ul></div>

</span></td>

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<tr valign="top"><td colspan="2"><span id="geo2r"></span> <span id="rnaseq_counts"></span></td></tr>

<tr bgcolor="#eeeeee" valign="top"><td>Submission date</td>

<td>Nov 29, 2024</td>

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<tr bgcolor="#eeeeee" valign="top"><td>Last update date</td>

<td>Apr 09, 2025</td>

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<tr bgcolor="#eeeeee" valign="top"><td>Contact name</td>

<td>Vera Helena Jepsen</td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">E-mail(s)</td>

<td><a href="mailto:VeraHelena.Jepsen@med.uni-duesseldorf.de">VeraHelena.Jepsen@med.uni-duesseldorf.de</a><br></td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">Organization name</td>

<td style="text-align: justify">University Hospital Düsseldorf<br></td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">Street address</td>

<td style="text-align: justify">Moorenstraße 5<br></td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">City</td>

<td style="text-align: justify">Düsseldorf</td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">ZIP/Postal code</td>

<td style="text-align: justify">40225</td>

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<tr bgcolor="#eeeeee" valign="top"><td nowrap="">Country</td>

<td style="text-align: justify">Germany</td>

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<tr valign="top"><td nowrap="">&nbsp;</td>

<td></td>

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<tr valign="top"><td>Platforms (1)</td>

<td onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_recenter)"><table cellpadding="3" style="position:relative;top:-5px;left:-5px"><tbody><tr><td valign="top"><a href="/geo/query/acc.cgi?acc=GPL34281" onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_recenter)">GPL34281</a></td>

<td valign="top">Illumina NovaSeq X (Homo sapiens)</td>

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