Progression of RAS-Mutant Leukemia during RAF Inhibitor Treatment

被引：194

作者：

Callahan, Margaret K. ^{[4
]}

Rampal, Raajit ^{[4
]}

Harding, James J. ^{[4
]}

Klimek, Virginia M. ^{[4
]}

Chung, Young Rock ^{[2
]}

Merghoub, Taha ^{[4
]}

Wolchok, Jedd D. ^{[4
]}

Solit, David B. ^{[2
,4
]}

Rosen, Neal ^{[3
,4
]}

Abdel-Wahab, Omar ^{[2
,4
]}

Levine, Ross L. ^{[2
,4
]}

Chapman, Paul B. ^{[1
,4
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, Melanoma & Sarcoma Serv, New York, NY 10065 USA

[2] Ludwig Inst Canc Res, Human Oncol & Pathogenesis Program, New York, NY USA

[3] Ludwig Inst Canc Res, Mol Pharmacol & Chem Program, New York, NY USA

[4] Weill Cornell Med Coll, New York, NY USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2012年 / 367卷 / 24期

关键词：

CHRONIC MYELOMONOCYTIC LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; METASTATIC MELANOMA; PARADOXICAL ACTIVATION; IMPROVED SURVIVAL; MEK INHIBITION; B-RAF; BRAF; MUTATIONS; V600E;

D O I：

10.1056/NEJMoa1208958

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2316 / 2321

页数：6

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