A panel study of genetic aberrations of chronic lymphocytic leukaemia using a fluorescence in-situ hybridisation

Abstract

Chronic lymphocytic leukaemia (CLL) is the commonest leukaemia among the adult population in Western countries. The morphologic features and immunophenotype of CLL are well characterised and fairly uniform. Yet the disease is highly variable in its clinical course. Reliable prognostic indicators to guide clinical management are clearly in need. Studies mainly from Western series have have identified many chromosomal abnormalities in CLL that are of prognostic values. Among them deletions are particularly common. Fluorescence in-situ hybridisation (FISH) is a fast way to identify these chromosomal aberrations in CLL patients by using a panel of DNA-specific fluorescent probes. The commonest chromosomal abnormalities reported are deletions at chromosomes 6q23, 11q23, 13q14, 13q34, 17p13, and trisomy 12. A number of specific genes at these sites are implicated. Chronic lymphocytic leukaemia is relatively uncommon in Chinese. It is of importance to determine whether the chromosome abnormalities among Chinese are identical to the Western findings. In this study, FISH was performed using the specific probes: CEP 12, LSI D13S319 (13q14), LSI 13q34, LSI p53 (17p13), LSI ATM (11q23), MYB LSI 6q23 and Dual Break Apart 14q32 (Vysis Inc., Downers Grove, IL, USA). For each probe, 500 nuclei were scored. We studied 39 Chinese CLL patients (22 males and 17 females, average age 66.3 years) for these 7 abnormalities, including the 14q32 probe that detects translocation involving the immunoglobulin heavy chain gene. Notably, twenty seven cases (69.3%) showed FISH abnormalities. The most frequent change was deletion of 13q14 (35.9%), followed by trisomy 12(33.3%), breakage at 14q32 (25.6%), deletion of 13q34 (23.1%), deletion of 6q23 (17.9%), deletion of 17p13 (12.8%) and deletion of 11q23 (2.6%). The frequencies of FISH abnormalities were compared with data in Western series and the significance of these genetic aberrations discussed. The most frequent abnormality was a 13q14 deletion worldwide, which was detected in 14 cases (35.9%) among Chinese patients. Besides, the significance of trisomy 12 was shown as an association with CLL patients. Understanding the genomic aberrations in CLL will enhance diagnosis, prognostication and ultimately treatment of this disease.