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Srsf2P95H/+ mutation exacerbates Asxl1Y588XTg-induced leukemogenesis

ABSTRACT: Srsf2P95H/+ mutation exacerbates Asxl1Y588XTg-induced leukemogenesis

PROVIDER: PRJNA1002285 | ENA |

REPOSITORIES: ENA

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Srsf2P95H/+ mutation exacerbates Asxl1Y588XTg-induced leukemogenesis

Project description:Additional sex comb-like 1 (ASXL1) is frequently mutated in a spectrum of myeloid malignancies and is associated with poor prognosis. Cancer genome sequencing found that AXL1 mutations frequently co-occur with splicing factors’ mutations (SRSF2, U2AF1, ZRZR2 and SF3B1) in myeloid malignancies. Several studies have reported that Patients with both ASXL1 and splicing mutations have a significantly worse prognosis than those with a single type of mutation, but the mechanisms largely remain to be elucidated. Here we constructed an ASXL1 and SRSF2 co-mutated mouse model and found that Srsf2P95H/+ mutation exacerbated Asxl1Y588XTg-induced leukemogenesis. Mechanistically, the co-existence of ASXL1 mutation and SRSF2 mutation altered the function of hematopoietic stem and progenitor cells and resulted in skewed myeloid differentiation.

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Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis (RRBS)

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