Progression of RAS-mutant leukemia during RAF inhibitor treatment Journal Article
| Authors: | Callahan, M. K.; Rampal, R.; Harding, J. J.; Klimek, V. M.; Chung, Y. R.; Merghoub, T.; Wolchok, J. D.; Solit, D. B.; Rosen, N.; Abdel-Wahab, O.; Levine, R. L.; Chapman, P. B. |
| Article Title: | Progression of RAS-mutant leukemia during RAF inhibitor treatment |
| 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. Copyright © 2012 Massachusetts Medical Society. |
| Journal Title: | New England Journal of Medicine |
| Volume: | 367 |
| Issue: | 24 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2012-12-13 |
| Start Page: | 2316 |
| End Page: | 2321 |
| Language: | English |
| DOI: | 10.1056/NEJMoa1208958 |
| PROVIDER: | scopus |
| PUBMED: | 23134356 |
| PMCID: | PMC3627494 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 January 2013" - "CODEN: NEJMA" - "Source: Scopus" |
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