REARRANGEMENT OF THE 5'-CLUSTER REGION OF THE BCL2 GENE IN LYMPHOID NEOPLASM - A SUMMARY OF 9 CASES

Rearrangement of the BCL2 gene with the immunoglobulin (IG) genes is t he most frequent genetic abnormality in B cell lymphoid neoplasms. In the majority of cases, breakages occur at two breakpoint cluster regio ns; major breakpoint cluster (MBR) and minor cluster region (mcr). In a minority of cases with non-Hodgkin's lymphoma (NHL) and chronic lymp hocytic leukemia (CLL), rearrangements involving the 5' flanking regio n of the BCL2 (5'-BCL2) have been reported. Here, we investigated 196 patients with NHL and 31 with CLL, with regard to rearrangement of the BCL2 gene. Hybridization analyses using probes representing the three cluster regions revealed that a total of 57 patients had a rearrangem ent of the BCL2; 42 (73.7%) were within the MBR, seven (12.2%) were wi thin the mcr, and nine (15.8%) had a rearrangement at the 5'-BCL2. The nine patients with 5'-BCL2 rearrangement included two with follicular lymphoma, four with diffuse large cell lymphoma and immunoblastic var iant, two with leukemic phase of follicular lymphoma, and one with CLL . Comigration analysis with probes for the IG heavy chain gene (IGH), kappa-chain gene (IG kappa) and lambda-chain gene (IG lambda), demonst rated a 5'-BCL2/IGH junction at the J(H) region in four patients with NHL derived from follicular center B cell. Thus, the 5' flanking regio n is a third cluster for recombination between the BCL2 and IGH, which is closely associated with the development of follicular center cell lymphoma, Molecular cloning of a 5'-BCL2/IGH junction demonstrated rec ombination of the two affected genes in divergent orientation. A 5'-BC L2/IG kappa junction was observed in two patients with immunoblastic l ymphoma, and one with CLL had a 5'-BCL2/IG lambda recombination. Two p atients, including one with a BCL2-MBR/J(H) junction, lacked obvious r ecombination of the 5'-BCL2 with IG genes, suggesting the presence of a deletion at the 5'-BCL2. Our findings demonstrated heterogeneity not only in clinicopathological presentation of B cell disease with rearr angement of 5'-BCL2, but also in molecular lesions resulting from the rearrangement.