Expression of cyclins D-type in B-chronic lymphoproliferative disorders

Abstract

Genetic alterations concerning the genes coding for cell cycle regulatory proteins have been described associated with B-chronic lymphoproliferative disorders. Most of them involve the pRb pathway and peculiarly the cyclin D1 protein that regulates the progression through the G1 phase and the G1 to S phase transition.1 In a recent paper, with the use of Northern blot technique, Suzuki and coworkers 2 described that cyclin D1 expression was observed in a majority of mantle cell lymphomas (MCL, 13/19), in a subset of B-chronic lymphocytic leukemias (B-CLL, 2/11) and in one out of six multiple myelomas (MM). In all cases but the MM, cyclin D1 expression was associated with the translocation t(11;14)(q13;q32) which joined the CCND1 locus encompassing the cyclin D1 coding gene with immunoglobulin heavy chain locus. Moreover, they described that cyclin D3 mRNA was ubiquitously expressed in B cell malignancies but restricted to cyclin D1 non-expressing cells when cyclin D2 mRNA was always present. We have also studied a series of 127 patients, with B-chronic lymphoproliferative disorders, using a very sensitive and reliable competitive RT-PCR technique, 3 followed by Western blotting. 4 In this series, cyclin D1 over-expression was detected in all patients with MCL (10/10), in a very few number of B-CLL (4/111), in hairy cell leukemias (HCL, 3/5) and in one out of one B-large cell lymphoma (BLCL). 4 We have now extended this study and analyzed by the same techniques 23 MCL, 174 B-CLL, 17 splenic lymphomas with villous lymphocytes (SLVL), 52 MM, four HCL, two B-prolymphocytic leukemias (B-PLL), five Waldenströ m's diseases (WD), three lymphoplasmocytic leukemias (LPL), and one follicular lymphoma (FL). By densitometric analysis of electrophoresed PCR fragments, 4 we have analyzed the relative intensity of each cyclin D product. We defined an over-expression of cyclin D1 when the intensity of cyclin D1 product was higher to those of cyclin D2 and D3

Real-Time RT-PCR Assay for Quantifying Cyclin D1 mRNA in B-Cell Non-Hodgkin's Lymphomas

“…Others have used RT-PCR methods to assess for cyclin D1 in MCL with results in general agreement with our own (18,23,(25)(26)(27)(28). In some of these studies, the presence or absence of cyclin D1 was considered the endpoint without quantification (23).…”

A subset of t(11;14) lymphoma with mantle cell features displays mutated IgVH genes and includes patients with good prognosis, nonnodal disease

“…It results in the juxtaposition of the BCL1 gene and the immunoglobulin heavy chain locus with consequent overexpression of cyclin D1. 1 The t (11;14) is the hallmark of mantle cell lymphoma (MCL), a disease also characterized by welldefined nodal histology and an immunophenotype typified by the strong expression of surface immunoglobulin, usually IgM and IgD, together with CD5, CD19, CD20, and CD79b. The translocation is not, however, exclusive to MCL, as it is found for example in myeloma, 2,3 a disease readily differentiated by its morphology and clinical picture.…”

Myeloma and the t(11;14)(q13;q32); evidence for a biologically defined unique subset of patients

“…17 Up-regulation of cyclin D1 is also detectable in multiple myeloma patients by immunohistochemistry in approximately 20% to 30%, [18][19][20] by Northern Blot in 17%, 21 and by reverse transcriptase-polymerase chain reaction in 35%. 22 The presence of the t(11;14)(q13;q32) and/or other 11q abnormalities in multiple myeloma patients has been associated with a worsened outcome and clinical features suggestive of aggressiveness when detected by karyotype analysis 23,24 and interphase FISH. 12 Biologic and pathologic features, including lymphoplasmacytic morphology and increased numbers of circulating plasma cells, have been suggested to be associated with the presence of this translocation.…”