Progression of RAS-mutant leukemia during RAF inhibitor treatment. uri icon

Overview

abstract

  • Vemurafenib, a selective RAF inhibitor, extends survival among patients with BRAF V600E-mutant melanoma. Vemurafenib inhibits ERK signaling in BRAF V600E-mutant cells but activates ERK signaling in BRAF wild-type cells. This paradoxical activation of ERK signaling is the mechanistic basis for the development of RAS-mutant squamous-cell skin cancers in patients treated with RAF inhibitors. We report the accelerated growth of a previously unsuspected RAS-mutant leukemia in a patient with melanoma who was receiving vemurafenib. Exposure to vemurafenib induced hyperactivation of ERK signaling and proliferation of the leukemic cell population, an effect that was reversed on drug withdrawal.

publication date

  • November 7, 2012

Research

keywords

  • Genes, ras
  • Indoles
  • Leukemia, Myelomonocytic, Chronic
  • Melanoma
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins B-raf
  • Sulfonamides

Identity

PubMed Central ID

  • PMC3951999

Scopus Document Identifier

  • 84871037064

Digital Object Identifier (DOI)

  • 10.1056/NEJMoa1208958

PubMed ID

  • 23134356

Additional Document Info

volume

  • 367

issue

  • 24