REARRANGEMENT OF THE BCL6 GENE IN B-CELL LYMPHOID NEOPLASMS - COMPARISON WITH LYMPHOMAS ASSOCIATED WITH BCL2 REARRANGEMENT

We report a series of B-cell neoplasms with regard to rearrangement of the BCL6 gene on chromosome band 3q27. Southern blot analysis using p robes from the major translocation cluster (MTC) region of the BCL6 re vealed rearrangement in 21/197 patients (10 . 7%) with B-cell neoplasm s studied at presentation, and 11/25 patients (44%) first studied at r elapse. In non-Hodgkin's lymphoma (NHL) studied at diagnosis, rearrang ements of the BCL6 gene were not closely associated with a specific hi stopathologic subtype but distributed in subcategories in the Working Formulation. The incidence in follicular lymphoma was 12 . 1%, with si gnificantly higher frequency in mixed and large cell subtypes, and tha t in diffuse aggressive lymphoma was 14 . 1%. Comigration analysis usi ng probes from the immunoglobulin genes revealed association of the BC L6 gene with one of the three immunoglobulin loci in 9/25 cases analys ed. A comparative study between NHL associated either with BCL2 or BCL 6 rearrangement showed that advanced disease and bone marrow involveme nt were more frequent in BCL2(+) NHL. In contrast, extranodal involvem ent was more frequently observed in the BCL6(+) NHL. The survival curv e of BCL6(+) NHL was characterized by a rapid decline followed by a pl ateau. Of the total of 32 BCL6(+) patients, six carried both BCL2 and BCL6 rearrangements; five of these six showed clinicopathological prop erties characteristic of follicular lymphoma, suggesting that the pres ence of the two genetic abnormalities does not necessarily have synerg istic effects on malignant phenotypes. The high level of BCL6 expressi on in follicular lymphoma cell lines carrying a BCL2 rearrangement sug gests that the deregulated BCL2 gene may have an effect on the develop ment of genetic abnormalities of the BCL6 gene. The present study sugg ests that BCL6 gene rearrangement is primarily involved in large cell lymphoma irrespective of growth pattern of neoplastic cells, and that BCL6(+)BCL2(-) NHL could be curable with modern intensive chemotherapy .