High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias

Abstract

To understand the genetic mechanisms driving variant and IGHV4-34-expressing hairy-cell leukemias, we performed whole-exome sequencing of leukemia samples from ten affected individuals, including six with matched normal samples. We identified activating mutations in the MAP2K1 gene (encoding MEK1) in 5 of these 10 samples and in 10 of 21 samples in a validation set (overall frequency of 15/31), suggesting potential new strategies for treating individuals with these diseases.

Figure 1. Distribution of mutations in MAP2K1

Schematic of the MEK1 protein and MAP2K1 gene structure. Somatic mutations identified in variant and IGHV4-34 expressing hairy cell leukemia samples cluster in exons 2 and 3 encoding the N-terminal auto-regulatory domain. Triangles above the protein indicate substitutions and the bar below indicates the in-frame deletion.