Overexpression of the signaling coordinator GAB2 can play an important role in acute myeloid leukemia progression.

ABSTRACT: Mutations that initiate acute myeloid leukemia (AML) can cause clonal expansion without transformation (clonal hematopoiesis). Cooperating mutations, usually in signaling genes, are needed to cause overt disease, but these may require a specific fitness state to be tolerated. Here, we show that nearly all AMLs arising in a mouse model expressing 2 common AML-initiating mutations (Dnmt3aR878H and Npm1cA) acquired a single copy amplification of chromosome 7 (chr7), followed by activating mutations in signaling genes. We show that overexpression of a single gene on chr7 (Gab2, which coordinates signaling pathways) was tolerated in the presence of the Npm1cA mutation, could accelerate the development of AML, and was important for the survival of fully transformed AML cells. GAB2 is likewise ov

SUBMITTER: Kramer MH 

PROVIDER: S-EPMC12578389 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature