MEK1 is required for the development of NRAS-driven leukemia.

ABSTRACT: The dual-specificity kinases MEK1 and MEK2 act downstream of RAS/RAF to induce ERK activation, which is generally considered protumorigenic. Activating MEK mutations have not been discovered in leukemia, in which pathway activation is caused by mutations in upstream components such as RAS or Flt3. The anti-leukemic potential of MEK inhibitors is being tested in clinical trials; however, downregulation of MEK1 promotes Eμ-Myc-driven lymphomagenesis and MEK1 ablation induces myeloproliferative disease in mice, raising the concern that MEK inhibitors may be inefficient or counterproductive in this context. We investigated the role of MEK1 in the proliferation of human leukemic cell lines and in retroviral models of leukemia. Our data show that MEK1 suppression via RNA interference and genomic

SUBMITTER: Nowacka JD 

PROVIDER: S-EPMC5348309 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature