PRAD-1/cyclin D1 gene overexpression in chronic lymphoproliferative disorders: a highly specific marker of mantle cell lymphoma

Abstract

The t(11;14)(q13;q32) translocation and its molecular counterpart bcl-1 rearrangement are frequently associated with mantle cell lymphomas (MCLs) and only occasionally with other variants of B-cell lymphoid malignancies. This translocation seems to activate the expression of PRAD-1/cyclin D1 gene located downstream from the major breakpoint cluster region of this rearrangement. However, the possible overexpression of this gene in other lymphoproliferative disorders independently of bcl-1 rearrangement is unknown. We have examined the overexpression of PRAD-1 gene in a large series of 142 lymphoproliferative disorders including 20 MCLs by Northern blot analysis. Cytogenetic and/or bcl-1 rearrangement analysis with 2 probes (MTC, p94PS) were performed in 28 cases. Strong PRAD-1 overexpression was observed in 19 of the 20 MCLs including 3 gastrointestinal forms and 4 blastic variants. t(11;14) and/or bcl-1 rearrangement was detected in 6 of the 12 MCLs examined. No correlation was found between the different levels of mRNA expression and the pathologic characteristics of the lymphoma. Among chronic lymphoproliferative disorders other than MCL, only 1 atypical chronic lymphocytic leukemia (CLL) with a t(11;14) translocation and bcl-1 rearrangement and the 2 hairy cell leukemias (HCLs) analyzed showed upregulation of PRAD-1 gene. The expression in the 2 HCLs was lower than in MCL, and no bcl-1 rearrangement was observed. These findings indicate that PRAD-1 overexpression is a highly sensitive and specific molecular marker of MCL but it may also be upregulated in some B-CLLs and in HCL.