{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:07:31Z","timestamp":1791893251415,"version":"4.3.4"},"reference-count":63,"publisher":"American Society of Hematology","issue":"7","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,13]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>IDH1 and IDH2 are frequently mutated in various cancers, including acute leukemias. However, the distinct mechanisms by which mutant IDH1 or IDH2 drive hematopoietic neoplasms remain poorly understood. Here, we analyzed DNA methylation in IDH1- and IDH2-mutant acute myeloid leukemia and found neutrophil lineage-specific epigenetic alterations in IDH1-mutant patients that went along with severely impaired neutrophil differentiation. Transcriptional analysis of normal hematopoiesis in humans and mice revealed a strong physiological upregulation of IDH1\/Idh1 in myeloid progenitors. To study the functional effects of Idh1 mutations on hematopoiesis in a preleukemic setting, we used a genetically engineered inducible mouse model expressing a heterozygous Idh1 mutation under control of the endogenous promotor. Our study revealed a cell-intrinsic block in neutrophil differentiation caused by repression of myeloid transcription programs in neutrophil progenitors. This included impaired expression of Cebpe, which encodes a key transcription factor regulating neutrophil differentiation. Reactivation of Cebpe expression, by overexpression of its upstream regulator Cebpa or following treatment with hypomethylating agents, restored differentiation, indicating that the differentiation block is reversible. In summary, we found a reversible, preleukemic impairment of neutrophil differentiation in IDH1-mutant hematopoiesis that correlates with elevated IDH1 expression in myeloid progenitors and likely explains the strong association of IDH1 mutations with myeloid neoplasms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025031268","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:01:46Z","timestamp":1779886906000},"page":"867-881","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":2,"title":["Mutant IDH1 blocks neutropoiesis by repressing myeloid progenitor programs"],"prefix":"10.1182","volume":"148","author":[{"given":"Mariam","family":"Hakobyan","sequence":"first","affiliation":[{"name":"1Section of Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center, Heidelberg, Germany"},{"name":"2National Center for Tumor Diseases Heidelberg, a partnership between German Cancer Research Center and Heidelberg University Hospital, Heidelberg, Germany"},{"name":"3Faculty of Biosciences, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Langstein","sequence":"additional","affiliation":[{"name":"1Section of Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center, Heidelberg, Germany"},{"name":"2National Center for Tumor Diseases Heidelberg, a partnership between German Cancer Research Center and Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Ramos Medina","sequence":"additional","affiliation":[{"name":"1Section of Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center, Heidelberg, Germany"},{"name":"2National Center for Tumor Diseases Heidelberg, a partnership between German Cancer Research Center and Heidelberg University Hospital, Heidelberg, Germany"},{"name":"3Faculty of Biosciences, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emely","family":"Kleinert","sequence":"additional","affiliation":[{"name":"1Section of Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center, Heidelberg, Germany"},{"name":"2National Center for Tumor Diseases Heidelberg, a partnership between German Cancer Research Center and Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9778-9698","authenticated-orcid":false,"given":"Maximilian","family":"Sch\u00f6nung","sequence":"additional","affiliation":[{"name":"1Section of Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center, Heidelberg, Germany"},{"name":"2National Center for Tumor Diseases Heidelberg, a partnership between German Cancer Research Center and Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4072-4658","authenticated-orcid":false,"given":"Mark","family":"Hartmann","sequence":"additional","affiliation":[{"name":"1Section of Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center, Heidelberg, Germany"},{"name":"2National Center for Tumor Diseases Heidelberg, a partnership between German Cancer Research Center and Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4985-1231","authenticated-orcid":false,"given":"Hannah","family":"Rohdjess","sequence":"additional","affiliation":[{"name":"1Section of Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center, Heidelberg, Germany"},{"name":"2National Center for Tumor Diseases Heidelberg, a partnership between German Cancer Research Center and Heidelberg University Hospital, Heidelberg, Germany"},{"name":"3Faculty of Biosciences, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Wojtarowicz","sequence":"additional","affiliation":[{"name":"1Section of Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center, Heidelberg, Germany"},{"name":"2National Center for Tumor Diseases Heidelberg, a partnership between German Cancer Research Center and Heidelberg University Hospital, Heidelberg, 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