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BRAF kinase domain mutations are present in a subset of chronic myelomonocytic leukemia with wild‐type RAS
Author(s) -
Zhang Liping,
Singh Rajesh R.,
Patel Keyur P.,
Stingo Francesco,
Routbort Mark,
You M. James,
Miranda Roberto N.,
GarciaManero Guillermo,
Kantarjian Hagop M.,
Medeiros L. Jeffrey,
Luthra Rajyalakshmi,
Khoury Joseph D.
Publication year - 2014
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23652
Subject(s) - neuroblastoma ras viral oncogene homolog , kras , chronic myelomonocytic leukemia , missense mutation , cancer research , exon , medicine , mutation , mapk/erk pathway , myeloid leukemia , kinase , biology , oncology , gene , genetics , myelodysplastic syndromes , bone marrow
The frequency of RAS mutations in chronic myelomonocytic leukemia (CMML) suggests that activation of the MAPK pathway is important in CMML pathogenesis. Accordingly, we hypothesized that mutations in other members of the MAPK pathway might be overrepresented in RAS wt CMML. We performed targeted next generation sequencing analysis on 70 CMML patients with known RAS mutation status. The study group included 37 men and 33 women with a median age of 67.8 years (range, 28–86 years). Forty patients were RAS wt and 30 were RAS mut ; the latter included KRAS = 17; NRAS = 12; KRAS + NRAS = 1. Five patients (7.1% of total group; 12.5% of RAS wt group) with RAS wt had kinase domain BRAF mutations. The BRAF mutations were of missense type and involved exon 11 in one patient and exon 15 in four patients. All BRAF mut patients had CMML‐1 with low‐risk cytogenetic findings. Two (40%) of the five patients with BRAF mut patients transformed to acute myeloid leukemia during follow‐up. In summary, we demonstrate that a subset of patients with RAS wt CMML harbors BRAF kinase domain mutations that are potentially capable of activating the MAPK signaling pathway. Am. J. Hematol. 89:499–504, 2014. © 2014 Wiley Periodicals, Inc.