Functional characterization of cooperating MGA mutations in RUNX1::RUNX1T1 acute myeloid leukemia.

ABSTRACT: MGA (Max-gene associated) is a dual-specificity transcription factor that negatively regulates MYC-target genes to inhibit proliferation and promote differentiation. Loss-of-function mutations in MGA have been commonly identified in several hematological neoplasms, including acute myeloid leukemia (AML) with RUNX1::RUNX1T1, however, very little is known about the impact of these MGA alterations on normal hematopoiesis or disease progression. We show that representative MGA mutations identified in patient samples abolish protein-protein interactions and transcriptional activity. Using a series of human and mouse model systems, including a newly developed conditional knock-out mouse strain, we demonstrate that loss of MGA results in upregulation of MYC and E2F targets, cell cycle genes, mTOR

SUBMITTER: Thomas ME 

PROVIDER: S-EPMC11073986 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature