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

Irons, Richard D.; Le, Anh; Bao, Liming; Zhu, Xiongzeng; Ryder, John; Wang, Xiao Qin; Ji, Meirong; Chen, Yan; Wu, Xichun; Lin, Guowei

doi:10.1016/j.leukres.2008.12.021

« Previous Next »Leukemia Research
Volume 33, Issue 12 , Pages 1599-1603, December 2009

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

Richard D. Irons
- Fudan-Cinpathogen Clinical and Molecular Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, CO, USA
- Department of Pathology, School of Medicine, University of Colorado Denver, CO, USA
- Corresponding author at: Fudan-Cinpathogen Clinical and Molecular Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China. Tel.: +1 303 381 2543; fax: +1 303 724 3673.
Anh Le
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, CO, USA
Liming Bao
- Fudan-Cinpathogen Clinical and Molecular Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center and College of Medicine, University of Cincinnati, OH, USA
Xiongzeng Zhu
- Department of Pathology, Cancer Hospital, Fudan University, Shanghai, China
John Ryder
- Department of Pathology, School of Medicine, University of Colorado Denver, CO, USA
Xiao Qin Wang
- Fudan-Cinpathogen Clinical and Molecular Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
- Huashan Hospital, Fudan University, Shanghai, China
Meirong Ji
- Huashan Hospital, Fudan University, Shanghai, China
Yan Chen
- Fudan-Cinpathogen Clinical and Molecular Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
Xichun Wu
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center and College of Medicine, University of Cincinnati, OH, USA
Guowei Lin
- Huashan Hospital, Fudan University, Shanghai, China

Received 22 December 2008; received in revised form 22 December 2008; accepted 29 December 2008. published online 07 March 2011.

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. IgV_H gene usage was non-random with over-representation of V_H4-34, V_H3-23 and a previously unreported increase in V_H3-48 gene use. Somatic hypermutation (SHM) of IgV_H germline sequences was observed in 56.5% of cases with stereotyped patterns of SHM observed in V_H4-34 heavy chain complimentary-determining (HCDR1) and framework region CFR2 sequences. These findings in a Chinese population suggest subtle geographical differences in IgV_H 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. IgV_H gene mutation status was a significant predictor of initial survival in CLL/SLL. However, an influence of karyotype on prognosis was not observed.