TET2 lesions enhance the aggressiveness of CEBPA-mutant acute myeloid leukemia by rebalancing GATA2 expression.

ABSTRACT: The myeloid transcription factor CEBPA is recurrently biallelically mutated (i.e., double mutated; CEBPA^DM) in acute myeloid leukemia (AML) with a combination of hypermorphic N-terminal mutations (CEBPA^NT), promoting expression of the leukemia-associated p30 isoform, and amorphic C-terminal mutations. The most frequently co-mutated genes in CEBPA^DM AML are GATA2 and TET2, however the molecular mechanisms underlying this co-mutational spectrum are incomplete. By combining transcriptomic and epigenomic analyses of CEBPA-TET2 co-mutated patients with models thereof, we identify GATA2 as a conserved target of the CEBPA-TET2 mutational axis, providing a rationale for the mutational spectra in CEBPA^DM AML. Elevated CEBPA levels, driven by CEBPA^NT<

SUBMITTER: Heyes E 

PROVIDER: S-EPMC10550934 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature