Chen Lijuan, Zhang Yaping, Zheng Wenjuan, Wu Yujie, Qiao Chun, Fan Lei, Xu Wei, Li Jianyong
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
Leuk Res. 2008 Oct;32(10):1491-8. doi: 10.1016/j.leukres.2008.02.005. Epub 2008 Mar 21.
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.
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.
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.
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.
亚洲国家慢性淋巴细胞白血病（CLL）的发病率低于西方国家，在西方国家CLL是最常见的白血病。它是一种临床异质性疾病，生存期从几个月到几十年不等。免疫球蛋白可变重链（IgVH）基因的突变状态显著改善了疾病进展风险的预测。我们调查了中国CLL患者中IgVH基因表达的频率和突变状态。
采用多重逆转录聚合酶链反应（RT-PCR）研究IgVH基因片段的使用情况和突变状态，并分析65例CLL患者中IgVH体细胞突变状态与CD38和ζ链相关蛋白激酶70（ZAP-70）表达之间的关系。
45例（69.2%）患者的IgVH发生突变，20例（30.8%）未发生突变。最常表达的VH基因家族是VH3（47.7%），其次是VH4（40%）、VH1（6.2%）、VH2（4.6%）和VH7（1.5%），未检测到VH5或VH6基因家族的表达。在西方CLL中常见过度使用的VH1-69和VH3-21在我们的队列中表达很低。IgVH基因突变状态与CD38的表达显著相关。
与西方患者相比，中国CLL患者IgVH基因家族的频率存在显著差异，提示种族和/或环境因素参与了CLL疾病的发生。它们的表达可能是识别IgVH突变的简单可靠指标。
