Characterization of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Shanghai, China: Molecular and cytogenetic characteristics, IgV gene restriction and hypermutation patterns

• Published in: Leukemia research Vol. 33; no. 12; pp. 1599 - 1603
• Main Authors: Irons, Richard D, Le, Anh, Bao, Liming, Zhu, Xiongzeng, Ryder, John, Wang, Xiao Qin, Ji, Meirong, Chen, Yan, Wu, Xichun, Lin, Guowei
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2009
• Subjects: 14q32/IGH; Adult; Aged; Base Sequence; China; Chronic lymphocytic leukemia; Cytogenetics; DNA Primers; Female; Fluorescence in situ hybridization; Genes, Immunoglobulin; Hematology, Oncology and Palliative Medicine; Humans; IgV genes; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Male; Middle Aged; Mutation; Small lymphocytic lymphoma; Somatic hypermutation; China; Chronic lymphocytic leukemia; Somatic hypermutation; Small lymphocytic lymphoma; Fluorescence in situ hybridization; Cytogenetics; IgV genes; 14q32/ IGH; 14q32/IGH
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2008.12.021

Abstract The clinical, cytogenetic and molecular features of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), a disease previously considered to be rare in Asia, were examined in consecutive series of 70 cases diagnosed by our laboratory over a 30-month period. Clonal abnormalities were observed in 80% of CLL/SLL cases using a combination of conventional cytogenetic and fluorescence in situ hybridization (FISH) analysis. Those involving 14q32/ IGH were the most frequent (24 cases), followed by trisomy 12 and 11q abnormalities. IgVH gene usage was non-random with over-representation of VH 4-34, VH 3-23 and a previously unreported increase in VH 3-48 gene use. Somatic hypermutation (SHM) of IgVH germline sequences was observed in 56.5% of cases with stereotyped patterns of SHM observed in VH 4-34 heavy chain complimentary-determining (HCDR1) and framework region CFR2 sequences. These findings in a Chinese population suggest subtle geographical differences in IgVH gene usage while the remarkably specific pattern of SHM suggest that a relatively limited set of antigens may be involved in the development of this disease worldwide. IgVH gene mutation status was a significant predictor of initial survival in CLL/SLL. However, an influence of karyotype on prognosis was not observed.