Distinctive IgVH gene segments usage and mutation status in Chinese patients with chronic lymphocytic leukemia

Leuk Res. 2008 Oct;32(10):1491-8. doi: 10.1016/j.leukres.2008.02.005. Epub 2008 Mar 21.

Abstract

Background and objectives: The incidence of chronic lymphocytic leukemia (CLL) in Asian countries is lower than that in the Western ones, where CLL is the most common leukemia. It is a clinically heterogeneous disease, with survival ranging from a few months to decades. The mutation status of the immunoglobulin variable heavy chain (IgVH) gene has significantly improved prediction of the risk for disease progression. We investigated the frequency and mutation status of IgVH gene expression in Chinese patients with CLL.

Methods: IgVH gene segments usage and mutation status were investigated by multiplex RT-PCR, and the relationship between IgVH somatic mutation status and the expression of CD38 and ZAP-70 was analyzed in 65 CLL patients.

Results: Forty-five (69.2%) patients had mutated IgVH, and 20 (30.8%) had unmutated IgVH. The most frequently expressed VH gene family was found to be VH3 (47.7%) followed by VH4 (40%), VH1 (6.2%), VH2 (4.6%) and VH7 (1.5%), with no expression of VH5 or VH6 gene families. VH1-69 and VH3-21 which commonly overused in Western CLL were very low in our cohort. IgVH gene mutation status was significantly associated with the expression of CD38.

Conclusions: 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. The expression of them may be simple and reliable surrogates for the identification of IgVH mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People / genetics
  • Biomarkers, Tumor / metabolism
  • China
  • Chromosome Aberrations
  • Female
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genes, Immunoglobulin Heavy Chain*
  • Humans
  • Immunoglobulin Variable Region / genetics
  • In Situ Hybridization, Fluorescence
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / ethnology
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Male
  • Middle Aged
  • Somatic Hypermutation, Immunoglobulin*
  • ZAP-70 Protein-Tyrosine Kinase / metabolism

Substances

  • Biomarkers, Tumor
  • Immunoglobulin Variable Region
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
  • ADP-ribosyl Cyclase 1