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

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...

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Bibliographic Details
Published in:Leukemia research 2009-12, Vol.33 (12), p.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: Article
Language:English
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
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Summary: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.
ISSN:0145-2126
1873-5835
DOI:10.1016/j.leukres.2008.12.021