Affiliation:
1. From the Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK; and the Molecular Immunology Department, Tenovus Research Laboratory, Southampton General Hospital, Southampton, UK.
Abstract
Despite having several characteristics of naı̈ve B cells, chronic lymphocytic leukemia (CLL) cells have been shown in some cases to have somatically mutated Ig variable region genes, indicating that the cell of origin has passed through the germinal center. A previous study of patients with CLL found an association between lack of somatic mutation and trisomy 12 and, therefore, possibly with a less favorable prognosis. We have sequenced the Ig VH genes of the tumor cells of 84 patients with CLL and correlated our findings with clinical features. A total of 38 cases (45.2%) showed ≥ 98% sequence homology with the nearest germline VH gene; 46 cases (54.8%) showed >2% somatic mutation. Unmutated VH genes were significantly associated with V1-69 and D3-3 usage, with atypical morphology; isolated trisomy 12, advanced stage and progressive disease. Survival was significantly worse for patients with unmutated VH genes irrespective of stage. Median survival for stage A patients with unmutated VH genes was 95 months compared with 293 months for patients whose tumors had mutated VHgenes (P = .0008). The simplest explanation is that CLL comprises 2 different diseases with different clinical courses. One, arising from a memory B cell, has a benign course, the other, arising from a naı̈ve B cell, is more malignant.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Reference34 articles.
1. The immunological profile of B cell disorders and proposal of a scoring system for the diagnosis of CLL.;Matutes;Leukemia,1994
2. Expression of the immunoglobulin associated protein B29 in B cell disorders with the monoclonal antibody SN8 (CD79b).;Zomas;Leukemia,1996
3. Discrimination of human leukemia subtypes by flow cytometric analysis of cellular DNA and RNA.;Andreef;Blood,1980
4. Expression of the bcl-2 oncogene protein is not specific for the 14;18 chromosomal translocation.;Pezella;Am J Pathol,1990
5. Leu-1+ (CD5+) B cells. A major lymphoid subpopulation in human fetal spleen.;Antin;J Immunol,1986
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