Distinctive IgVH Gene Segments Usage and Mutation Status in Chinese Patients with Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by the relentless accumulation of monoclonal B cells with the appearance of small mature lymphocytes and a characteristic CD5 and CD19 co-expression immunophenotype. The incidence of CLL in Asian countries is lower than that in the Western ones, where CLL is the most common leukemia. To evaluate the frequency and mutation status of immunoglobulin (Ig) variable heavy chain gene (IgVH) expression in Chinese patients with CLL. We investigated IgVH gene segments usage and mutation status by multiplex RT-PCR in 52 CLL patients, and analyzed the relationship between IgVH somatic mutation status and the expression of CD38, ZAP-70 and CLLU1. 38 patients had mutated IgVH, and 14 had unmutated IgVH. The most frequently expressed VH gene family was found to be VH3 (46.2%) followed by VH4 (40.4%), VH1 (5.8%), VH2 (5.8%) and VH7 (1.9%), with no expression of VH5 and VH6 gene families. VH1-69 and VH3-21 which commonly overused in Western CLL weren’t detected in our cohort. The frequency of IgVH gene families indicates significant difference in Chinese CLL patients compared with Western patients, suggesting involvement of ethnic and/or environmental factors in CLL disease initiation. IgVH gene mutation status was significantly associated with the expression of CD38 and CLLU1. The expression of them may be simple and reliable surrogates for the identification of IgVH mutations.