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

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Abstract
Cyclin D1 participates in cell‐cycle control, in the progression through the G1 phase and in the transition from the G1 to the S phase. The CCND1 locus, located in 11q13, is amplified and cyclin‐D1 protein is over‐expressed 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 CCND1 locus and leads to cyclin‐D1 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‐D1 mRNA was expressed in patients with mantle‐cell lymphoma (MCL; 10/10), hairy‐cell leukemia (HCL; 3/5), B‐chronic lymphoid leukemia (B‐CLL; 4/111) and B large‐cell lymphoma (BLCL; 1/1). Densitometric analysis of RT‐PCR products and Western‐blot autoradiograms, in addition to cytogenetic data, indicated that activation of the cyclin‐D1 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 with gene activation by a translocation mechanism was detected in lymphoid cells with a normal karyotype. Moreover, we found a discrepancy between cyclin‐D1 mRNA and protein levels in MCL and B‐CLL, which suggested that some regulatory mechanisms acting at a post‐transcriptional level persist in tumor cells. Int. J. Cancer 83:230–234, 1999.