期刊
BLOOD
卷 123, 期 20, 页码 3152-3155出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-06-511139
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- Histiocytosis Association
- Boston Marathon Jimmy Fund Walk
- Stichting 1000 Kaarsjes voor Juultje
- Say Yes to Education foundation
The extracellular signal-regulated kinase (ERK) signaling pathway is activated in Langerhans cell histiocytosis (LCH) histiocytes, but only 60% of cases carry somatic activating mutations of BRAF. To identify other genetic causes of ERK pathway activation, we performed whole exome sequencing on purified LCH cells in 3 cases. One patient with wild-type BRAF alleles in his histiocytes had compound mutations in the kinase domain of ARAF. Unlike wild-type ARAF, this mutant was a highly active mitogen-activated protein kinase kinase in vitro and was capable of transforming mouse embryo fibroblasts. Mutant ARAF activity was inhibited by vemurafenib, a BRAF inhibitor, indicating the importance of fully evaluating ERK pathway abnormalities in selecting LCH patients for targeted inhibitor therapy.
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