Transcriptional and post-transcriptional mechanisms induce cyclin-D1 over-expression in B-chronic lymphoproliferative disorders

Cyclin DI participates in cell-cycle control, in the progression through th e G(1) phase and in the transition from the G(1) to the S phase. The CCND1 locus, located in 11q13, is amplified and cyclin-DI protein is over-express ed in a wide range of human solid tumors. In some B-lymphoid malignancies, the t(11;14)(q13;q32) translocation joins the Ig heavy-chain locus to the C CND1 locus and leads to cyclin-DI over-expression. In this study, a series of 127 patients presenting a B-chronic lymphoproliferative disorder (B-CLPD ) was analyzed using a competitive RT-PCR designed to detect cyclin-D1-mRNA over-expression. Cyclin-DI mRNA was expressed in patients with mantle-cell lymphoma(MCL; 10/10), hairy-cell leukemia (HCL; 3/5), B-chronic lymphoid l eukemia (B-CLL; 4/111)and B large-cell lymphoma(BLCL; Iii). Densitometric a nalysis of RT-PCR products and Western-blot autoradiograms, in addition to cytogenetic data, indicated that activation of the cyclin-DI gene occurred independently of the t(11;14)(q13; q32) translocation in patients with HCL, Indeed, a normal-sized protein of 36 kDa exhibiting a level incompatible w ith gene activation by a translocation mechanism was detected in lymphoid c ells with a normal karyotype, Moreover, we found a discrepancy between cycl in-DI mRNA and protein levels in MCL and B-CLL, which suggested that some r egulatory mechanisms acting at a post-transcriptional level persist in tumo r cells. (C) 1999 Wiley-Liss. Inc.