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The ASXL1-G643W variant accelerates the development of CEBPA mutant acute myeloid leukemia

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  1. Myelodysplastic syndrome patient-derived xenografts: from no options to many

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  2. KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Optimized EBMT transplant-specific risk score in myelodysplastic syndromes after allogeneic stem-cell transplantation

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Myelodysplastic syndrome patient-derived xenografts: from no options to many

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Heterozygous loss of Srp72 in mice is not associated with major hematological phenotypes

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ASXL1 is one of the most commonly mutated genes in myeloid malignancies, including Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). In order to further our understanding of the role of ASXL1 lesions in malignant hematopoiesis, we generated a novel knock-in mouse model carrying the most frequent ASXL1 mutation identified in MDS patients, p.G643WfsX12. Mutant mice did not display any major hematopoietic defects nor developed any apparent hematological disease. In AML patients, ASXL1 mutations co-occur with mutations in CEBPA and we therefore generated compound Cebpa and Asxl1 mutated mice. Using a transplantation model, we found that the mutated Asxl1 allele significantly accelerated disease development in a CEBPA mutant context. Importantly, we demonstrated that, similar to the human setting, Asxl1 mutated mice responded poorly to chemotherapy. This model therefore constitutes an excellent experimental system for further studies into the clinically important question of chemotherapy resistance mediated by mutant ASXL1.

Original languageEnglish
JournalHaematologica
ISSN0390-6078
DOIs
Publication statusPublished - 7 May 2020

ID: 60067627