PRAD-1 CYCLIN D1 GENE OVEREXPRESSION IN CHRONIC LYMPHOPROLIFERATIVE DISORDERS - A HIGHLY SPECIFIC MARKER OF MANTLE CELL LYMPHOMA

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 mal ignancies. 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 PR AD-1 gene in a large series of 142 lymphoproliferative disorders inclu ding 20 MCLs by Northern blot analysis. Cytogenetic and/or bcl-1 rearr angement analysis with 2 probes (MTC, p94PS) were performed in 28 case s. Strong PRAD-1 overexpression was observed in 19 of the 20 MCLs incl uding 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 cor relation was found between the different levels of mRNA expression and the pathologic characteristics of the lymphoma. Among chronic lymphop roliferative disorders other than MCL, only 1 atypical chronic lymphoc ytic leukemia (CLL) with a t(11;14) translocation and bcl-1 rearrangem ent 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, a nd no bcl-1 rearrangement was observed. These findings indicate that P RAD-1 overexpression is a highly sensitive and specific molecular mark er of MCL but it may also be upregulated in some B-CLLs and in HCL. (C ) 1994 by The American Society of Hematology.