Mutant <i>IDH1</i> cooperates with <i>NPM1c</i> or <i>FLT3</i>^ITD to drive distinct myeloid diseases and molecular outcomes.

ABSTRACT: In human acute myeloid leukemia (AML), mutations of isocitrate dehydrogenase-1 (IDH1) often co-occur with NPM1 mutations, and less frequently with FLT3 mutations. To investigate whether the effects of IDH1 mutation differ according to the specific co-occurring mutation, we generated two strains of double knock-in mutant mice. Idh1^R132H combined with Npm1c induced overt AML, whereas Idh1^R132H plus Flt3^ITD resulted in Flt3^ITD-driven myelo- or lymphoproliferation that was minimally affected by Idh1^R132H and rarely generated AML. Gene expression profiling revealed differences between Idh1^R132H;Npm1c cells and Idh1^R132H;Flt3</

SUBMITTER: Sakamoto T 

PROVIDER: S-EPMC12107087 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature