BRAF kinase domain mutations are present in a subset of chronic myelomonocytic leukemia with wild‐type RAS. Issue 5 (10th February 2014)

• Record Type: Journal Article
• Authors: Zhang, Liping; Singh, Rajesh R.; Patel, Keyur P.; Stingo, Francesco; Routbort, Mark; You, M. James; Miranda, Roberto N.; Garcia‐Manero, Guillermo; Kantarjian, Hagop M.; Medeiros, L. Jeffrey; Luthra, Rajyalakshmi; Khoury, Joseph D.
• Is Part Of: American journal of hematology. Volume 89:Issue 5(2014:May)
• Page Start: 499
• Page End: 504
• Publication Date: 2014-02-10
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.23652
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The frequency of <italic>RAS</italic> 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 <italic>RAS<sup>wt</sup></italic> CMML. We performed targeted next generation sequencing analysis on 70 CMML patients with known <italic>RAS</italic> 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 <italic>RAS<sup>wt</sup></italic> and 30 were <italic>RAS<sup>mut</sup></italic>; the latter included <italic>KRAS</italic> = 17; <italic>NRAS</italic> = 12; <italic>KRAS</italic> + <italic>NRAS</italic> = 1. Five patients (7.1% of total group; 12.5% of <italic>RAS<sup>wt</sup></italic> group) with <italic>RAS<sup>wt</sup></italic> had kinase domain <italic>BRAF</italic> mutations. The <italic>BRAF</italic> mutations were of missense type and involved exon 11 in one patient and exon 15 in four patients. All <italic>BRAF<sup>mut</sup></italic> patients had CMML‐1 with low‐risk cytogenetic findings. Two (40%) of the five patients with <italic>BRAF<sup>mut</sup></italic> patients transformed to acute myeloid leukemia during follow‐up. In summary, we demonstrate that a subset of patients with <italic>RAS<sup>wt</sup></italic> CMML harbors <italic>BRAF</italic> kinase domain mutations that are potentially capable of activating the MAPK signaling pathway. Am. J. Hematol. 89:499–504, 2014. © 2014 Wiley Periodicals, Inc.</p> </abstract>