Progression of RAS-mutant leukemia during RAF inhibitor treatment.
case_report · Level V
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- Record sourced from PubMed, PMID 23134356.
- Also identified by DOI 10.1056/NEJMoa1208958 and PMC identifier 3627494.
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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.
Medical subject headings
- Genes, ras
- Indoles
- Leukemia, Myelomonocytic, Chronic
- Melanoma
- Protein Kinase Inhibitors
- Proto-Oncogene Proteins B-raf
- Sulfonamides