DNA from 14 follicular and 42 diffuse B-cell lymphomas was examined using oligonucleotide primers specific for opposing sides of the IgH gene rearrangement on chromosome 14 (towards conserved VH and JH sequences) and opposing sides of the t(14;18) chromosomal translocation (towards the major breakpoint region of the bcl-2 gene on chromosome 18 and conserved JH sequence on chromosome 14).
Cytogenetic techniques were supplemented by molecular analysis using probes which recognize both the major and the minor breakpoint regions of the bcl-2 gene located on chromosome 18 (q21). t(14;18) was detected in 55 per cent of follicular and 27 per cent of diffuse B-cell lymphomas thought to be of follicle centre cell origin.
In this study, we investigated 34 cases of HD (10 LP, 14 NS, and 10 MC) for bcl-2 gene rearrangements to determine if this B-cell lymphoma-associated translocation also plays a role in the pathogenesis of HD.
The bcl-2 proto-oncogene, rearranged and deregulated in B-cell lymphomas bearing the t(14;18) translocation, encodes an inner mitochondrial membrane protein that blocks apoptotic cell death.
To investigate the role of the BCL-2 gene in Japanese patients with B-cell non-Hodgkin's lymphoma, karyotypic analysis, DNA analysis and clinical characterization were studied.
Cases of NLPHD differ from most low-grade follicular B-cell lymphomas in that they lack bcl-2 gene rearrangement and t(14;18) translocation at the major breakpoint region.
Less involvement of bcl-2 in Japanese B cell lymphoma may also be in part explainable by low susceptibility to bcl-2 rearrangement at the step of DH-JH recombination.
We conclude that abnormal expression of bcl-2 rather than structural alterations at codon 7 or 129 play an important role in the disordered growth and differentiation of follicular B-cell lymphoma.
Two of eight (25%) cases of follicular lymphoma but only one of the 34 (2.9%) cases of diffuse B-cell lymphoma had bcl-2 rearrangement that was detected by pFL-1 probe.
Antisense oligodeoxynucleotides specific for sequences in mRNAs from the B-cell lymphoma/leukemia-2 (BCL2) gene were used to inhibit the growth in culture of a human leukemia cell line, 697.
Moreover, the B-cell lymphomas were studied for the presence of the chromosomal translocations t(11;14) and t(14;18) using probes for bcl-1 and bcl-2 genes, respectively.
The putative oncogene bcl-2 is juxtaposed to the immunoglobulin heavy chain (Igh) locus by the t(14;18) chromosomal translocation typical of human follicular B-cell lymphomas.
These data indicate that primary cutaneous lymphomas of B-cell origin share morphological and phenotypic similarities with the nodal B-cell lymphomas of follicular histotype, are proliferating, and express in 45% of cases clear monoclonal immunoglobulin light chain; the molecular analysis confirms the B-cell derivation and the monoclonal nature of this neoplasia; it also shows that neither bcl-2 nor c-myc oncogenes are involved and that no inappropriate rearrangements of the T-cell receptor genes are found in this lymphoma.
The human bcl-2 gene is a oncogene candidate which is involved in the t(14;18) translocation specifically associated with follicular and diffuse B cell lymphomas.