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PRAD-1/cyclin D1 gene overexpression in chronic lymphoproliferative
disorders: a highly specific marker of mantle cell lymphoma
F Bosch, P Jares, E Campo, A Lopez-Guillermo, MA Piris, N Villamor, D Tassies, ES Jaffe, E Montserrat and C Rozman
Postgraduate School of Hematology, Farreras Valenti, Barcelona, Spain.
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.
Volume 84,
Issue 8,
pp. 2726-2732,
10/15/1994
Copyright © 1994 by The American Society of Hematology
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