CYCLIN-D1 OVEREXPRESSION IN NON-HODGKINS-LYMPHOMA WITH CHROMOSOME-11 BCL-1 REARRANGEMENT

Background: Approximately 70% of centrocytic (mantle-cell) lymphomas have the chromosomal translocation t(11; 14) (q13; q32) and associated rearrangements at the bcl-l breakpoint locus and at the cyclin D1 (PRAD1, CCND1) gene, thus implicating this gene in the pathogenesis of centrocytic lymphoma. In order to determine cyclin D1 expression in hematopoietic neoplasms with and without bcl-1 or cyclin D1 rearrangements, northern blot analysis was performed. Methods. Total RNA was isolated from peripheral blood cells of patients with hematopoietic neoplasms in leukemic phase, including three patients with B-cell lymphoma containing chromosome 11q13 bcl-1 rearrangements. Northern blots were hybridized with a cyclin D1 cDNA probe and the degree of mRNA expression determined. Results: Each of the bcl-1-rearranged cases showed high levels of cyclin Dl expression, whereas no expression was detected in RNA from samples of B-cell CLL, T-cell prolymphocytic leukemia, or acute nonlymphocytic leukemia which lacked bcl-1 or cyclin D1 rearrangement. Conclusions: Overexpression of cyclin D1, a G1 cyclin implicated in cell-cycle regulation, may play a critical role in the pathogenesis of t(11; 14)-positive lymphomas.