Molecular synergy underlies the co-occurrence patterns and phenotype of <i>NPM1</i>-mutant acute myeloid leukemia.

ABSTRACT: NPM1 mutations define the commonest subgroup of acute myeloid leukemia (AML) and frequently co-occur with FLT3 internal tandem duplications (ITD) or, less commonly, NRAS or KRAS mutations. Co-occurrence of mutant NPM1 with FLT3-ITD carries a significantly worse prognosis than NPM1-RAS combinations. To understand the molecular basis of these observations, we compare the effects of the 2 combinations on hematopoiesis and leukemogenesis in knock-in mice. Early effects of these mutations on hematopoiesis show that compound Npm1^cA/+;Nras^G12D/+ or Npm1^cA;Flt3^ITD share a number of features: Hox gene overexpression, enhanced self-renewal, expan

SUBMITTER: Dovey OM 

PROVIDER: S-EPMC5672315 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature