Oncogenic N-Ras Mitigates Oxidative Stress-Induced Apoptosis of Hematopoietic Stem Cells.

ABSTRACT: Leukemic relapse is believed to be driven by transformed hematopoietic stem cells (HSC) that harbor oncogenic mutations or have lost tumor suppressor function. Recent comprehensive sequencing studies have shown that mutations predicted to activate Ras signaling are highly prevalent in hematologic malignancies and, notably, in refractory and relapsed cases. To better understand what drives this clinical phenomenon, we expressed oncogenic Nras^G12D within the hematopoietic system in mice and interrogated its effects on HSC survival. N-Ras^G12D conferred a survival benefit to HSCs and progenitors following metabolic and genotoxic stress. This effect was limited to HSCs and early progenitors and was independent of autophagy and cell proliferation. N-Ras^G12D

SUBMITTER: Ney GM 

PROVIDER: S-EPMC8647627 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature