Missense Mutations in Myc Box I Influence Nucleocytoplasmic Transport to Promote Leukemogenesis.

ABSTRACT:

Purpose

Somatic missense mutations in the phosphodegron domain of the MYC gene (MYC Box I or MBI) are detected in the dominant clones of a subset of patients with acute myeloid leukemia (AML), but the mechanisms by which they contribute to AML are unknown.

Experimental design

To investigate the effects of MBI MYC mutations on hematopoietic cells, we employed a multi-omic approach to systematically compare the cellular and molecular consequences of expressing oncogenic doses of wild type, threonine-58 and proline-59 mutant MYC proteins in hematopoietic cells, and we developed a knockin mouse harboring the germline MBI mutation p.T58N in the Myc gene.

Results

Both wild-type and MBI mutant MYC proteins promote self-renewal programs and expand highly selected subpopulatio

SUBMITTER: Arthur NBJ 

PROVIDER: S-EPMC11326984 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature