{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Parsons TM"],"funding":["NIDDK NIH HHS","NHLBI NIH HHS","NCI NIH HHS"],"pubmed_abstract":["Myeloproliferative neoplasms (MPNs) are hematological diseases predominantly driven by the <i>JAK2</i> <sup>V617F</sup> mutation. Progression from chronic-phase MPN to secondary acute myeloid leukemia (sAML) is a severe complication that dramatically worsens disease prognosis. While progression to sAML is classically linked to MPN clones acquiring additional mutations, the absence of <i>JAK2</i> <sup>V617F</sup> in some cases of post-MPN sAML cases suggests alternative mechanisms of transformation. Utilizing patient samples and <i>in vivo</i> modeling, we establish that leukemic clones can emerge independently of <i>JAK2</i>-mutant cells and undergo positive selection in the pro-inflammatory MPN environment, leading to parallel disease evolution. Genetic and pharmacological inhibition of IL-12 and TNFα mitigates this competitive advantage. Our data establish a new paradigm and show that disease progression in MPN can arise from parallel acute myeloid leukemia (pAML) clones."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.09.23.678057"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12485877"],"repository":["biostudies-literature"],"pubmed_title":["&lt;i&gt;JAK2&lt;/i&gt; &lt;sup&gt;V617F&lt;/sup&gt; Myeloproliferative Neoplasms Support Parallel Evolution of Independent Leukemic Clones."],"pmcid":["PMC12485877"],"funding_grant_id":["R01 HL147978","R01 HL134952","P30 CA091842","R01 CA236819","K99 CA296777","R01 DK124883","T32 HL007088"],"pubmed_authors":["Raj IX","Challen GA","Oh ST","Young AL","Parsons TM","Arand J","Krishnan A","Cox M","O'Leary DR"],"additional_accession":[]},"is_claimable":false,"name":"&lt;i&gt;JAK2&lt;/i&gt; &lt;sup&gt;V617F&lt;/sup&gt; Myeloproliferative Neoplasms Support Parallel Evolution of Independent Leukemic Clones.","description":"Myeloproliferative neoplasms (MPNs) are hematological diseases predominantly driven by the <i>JAK2</i> <sup>V617F</sup> mutation. Progression from chronic-phase MPN to secondary acute myeloid leukemia (sAML) is a severe complication that dramatically worsens disease prognosis. While progression to sAML is classically linked to MPN clones acquiring additional mutations, the absence of <i>JAK2</i> <sup>V617F</sup> in some cases of post-MPN sAML cases suggests alternative mechanisms of transformation. Utilizing patient samples and <i>in vivo</i> modeling, we establish that leukemic clones can emerge independently of <i>JAK2</i>-mutant cells and undergo positive selection in the pro-inflammatory MPN environment, leading to parallel disease evolution. Genetic and pharmacological inhibition of IL-12 and TNFα mitigates this competitive advantage. Our data establish a new paradigm and show that disease progression in MPN can arise from parallel acute myeloid leukemia (pAML) clones.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-05-08T03:18:24.419Z","creation":"2026-05-08T03:10:27.35Z"},"accession":"S-EPMC12485877","cross_references":{"pubmed":["41040409"],"doi":["10.1101/2025.09.23.678057"]}}