Nuclear factor of activated T-cells, NFATC1, governs FLT3^ITD-driven hematopoietic stem cell transformation and a poor prognosis in AML.

ABSTRACT:

Background

Acute myeloid leukemia (AML) patients with a high allelic burden of an internal tandem duplication (ITD)-mutated FMS-like Tyrosine Kinase-3 (FLT3) have a dismal outcome. FLT3^ITD triggers the proliferation of the quiescent hematopoietic stem cell (HSC) pool but fails to directly transform HSCs. While the inflammatory transcription factor nuclear factor of activated T-cells 2 (NFAT2, NFATC1) is overexpressed in AML, it is unknown whether it plays a role in FLT3^ITD-induced HSC transformation.

Methods

We generated a triple transgenic mouse model, in which tamoxifen-inducible Cre-recombinase targets expression of a constitutively nuclear transcription factor NFATC1 to FLT3^ITD positive HSC. Emerging genotypes were phenotypically, biochem

SUBMITTER: Solovey M 

PROVIDER: S-EPMC6615262 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature