Gain of function of ASXL1 truncating protein in the pathogenesis of myeloid malignancies.

ABSTRACT: Additional Sex Combs-Like 1 (ASXL1) is mutated at a high frequency in all forms of myeloid malignancies associated with poor prognosis. We generated a Vav1 promoter-driven Flag-Asxl1^Y588X transgenic mouse model, Asxl1^Y588X Tg, to express a truncated FLAG-ASXL1^aa1-587 protein in the hematopoietic system. The Asxl1^Y588X Tg mice had an enlarged hematopoietic stem cell (HSC) pool, shortened survival, and predisposition to a spectrum of myeloid malignancies, thereby recapitulating the characteristics of myeloid malignancy patients with ASXL1 mutations. ATAC- and RNA-sequencing analyses revealed that the ASXL1^aa1-587 truncating protein expression results in more open chromatin in

SUBMITTER: Yang H 

PROVIDER: S-EPMC5774208 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature