Involvement of the BCL2 Gene in 131 Cases of Non-Hodgkin's B Lymphomas: Analysis of Correlations with Immunological Findings and Cell Cycle

The t(14;18) chromosomal translocation is widely recognized as a cytogenetic abnormality associated with follicular lymphomas, but estimates of its frequency in this type of lymphoma vary from less than 40% to almost 90% according to the geographic origin of the patients. Using two human genomic probes for major and minor breakpoint cluster regions mapping at chromosome 18q21, we have analysed 131 cases of B non-Hodgkin's lymphomas obtained from France, by the Southern blot technique. The genotypic study was complemented in most cases by immunophenotypic and cell kinetic analyses. The BCL2 gene located at 18q21 band was rearranged in 39 of 56 (70%) follicular lymphomas and in 9 of 74 (12%) diffuse lymphomas; probes for major and minor breakpoint regions detected two thirds and one third of the rearrangements respectively. Regarding the morphologic subtypes of follicular and diffuse lymphomas, no significant differences were observed irrespective of the probe used. Review of the literature showed that comparable results have been obtained previously using both cytogenetic and molecular approaches and our results support the view that the global incidence of the t(14;18)(q32;q21) translocation in follicular lymphomas is about 70% with wide geographic variations. The immunological study provides evidence for a significant correlation of BCL2 rearrangement with surface immunoglobulin gamma isotype expression and with the lack of reactivity of the malignant cells with an antibody against the CD5 cluster. In the cases where cell kinetics was analysed, we did not find any significant difference between the rate of proliferation and BCL2 rearrangement. These data should be compared with previously reported observations made in humans or in transgenic mice and enable us to propose a model accounting for the role of BCL2 in B cell tumorigenesis.