Transgenic IDH2^R172K and IDH2^R140Q zebrafish models recapitulated features of human acute myeloid leukemia.

ABSTRACT: Isocitrate dehydrogenase 2 (IDH2) mutations occur in more than 15% of cytogenetically normal acute myeloid leukemia (CN-AML) but comparative studies of their roles in leukemogenesis have been scarce. We generated zebrafish models of IDH2^R172K and IDH2^R140Q AML and reported their pathologic, functional and transcriptomic features and therapeutic responses to target therapies. Transgenic embryos co-expressing FLT3^ITD and IDH2 mutations showed accentuation of myelopoiesis. As these embryos were raised to adulthood, full-blown leukemia ensued with multi-lineage dysplasia, increase in myeloblasts and marrow cellularity and splenomegaly. The leukemia cells were transplantable into primary and secondary recipients and resulted in more aggressive disease. Tg(Runx1:

SUBMITTER: Wang D 

PROVIDER: S-EPMC10101851 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature