{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Eldfors S"],"funding":["NCI NIH HHS"],"pubmed_abstract":["<i>SRSF2</i> mutations occur in up to 25% of acute myeloid leukemia (AML) and 17% of myelodysplastic syndrome (MDS) cases and are associated with poor prognosis, yet no mutation-directed therapy exists. Here, we aimed to identify therapeutically targetable vulnerabilities in MDS/AML with <i>SRSF2</i> mutations. Ex vivo drug-sensitivity testing of bone marrow cells from AML patients and healthy donors showed that <i>SRSF2</i>-mutant cells are sensitive to inhibitors of CHK1, and WEE1 DNA damage response (DDR) kinases. To test causality, we engineered isogenic K562 cell line clones expressing <i>SRSF2</i> <sup>P95H/L/R</sup> mutations. RNA sequencing confirmed splicing aberrations characteristic of MDS/AML in these clones. We found that <i>SRSF2</i> <sup>P95H/L/R</sup> sensitize leukemia cel"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.10.06.680457"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12632562"],"repository":["biostudies-literature"],"pubmed_title":["Sensitivity to ATR-CHK1 pathway inhibition in AML/MDS is enhanced by &lt;i&gt;SRSF2&lt;/i&gt; mutations and reduced by RUNX1 loss."],"pmcid":["PMC12632562"],"funding_grant_id":["P50 CA171963"],"pubmed_authors":["Pastrana CC","Gilbert A","Graubert TA","Sharma V","Bertino A","Porkka K","Eldfors S","Rai S","Walter M","Hossan T"],"additional_accession":[]},"is_claimable":false,"name":"Sensitivity to ATR-CHK1 pathway inhibition in AML/MDS is enhanced by &lt;i&gt;SRSF2&lt;/i&gt; mutations and reduced by RUNX1 loss.","description":"<i>SRSF2</i> mutations occur in up to 25% of acute myeloid leukemia (AML) and 17% of myelodysplastic syndrome (MDS) cases and are associated with poor prognosis, yet no mutation-directed therapy exists. Here, we aimed to identify therapeutically targetable vulnerabilities in MDS/AML with <i>SRSF2</i> mutations. Ex vivo drug-sensitivity testing of bone marrow cells from AML patients and healthy donors showed that <i>SRSF2</i>-mutant cells are sensitive to inhibitors of CHK1, and WEE1 DNA damage response (DDR) kinases. To test causality, we engineered isogenic K562 cell line clones expressing <i>SRSF2</i> <sup>P95H/L/R</sup> mutations. RNA sequencing confirmed splicing aberrations characteristic of MDS/AML in these clones. We found that <i>SRSF2</i> <sup>P95H/L/R</sup> sensitize leukemia cel","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-10T03:10:37.017Z","creation":"2026-06-10T03:07:20.65Z"},"accession":"S-EPMC12632562","cross_references":{"pubmed":["41279606"],"doi":["10.1101/2025.10.06.680457"]}}