CYCLIN D1 PROTEIN EXPRESSION IN MANTLE CELL LYMPHOMA

Background: The t(11;14)(q13;q32) is a chromosomal abnormality usually associated with mantle cell (centrocytic) lymphomas, although it has occasionally been reported in other chronic lymphoproliferative disorders such as chronic lymphocytic leukemia, prolymphocytic leukemia, splenic lymphoma with villous lymphocytes, and multiple myeloma. This abnormality results in the translocation of the bcl-1 oncogene from chromosome 11 to the immunoglobulin heavy chain locus on chromosome 14. The bcl-1 oncogene is a member of the cyclin gene family, and high levels of cyclin D1 mRNA are consistently found in malignant B cell proliferations with t(11;14). Patients and methods: We examined cyclin D1 protein expression in 33 patients with low grade lymphoproliferative disorders and 2 patients with reactive hyperplasias by Western blot analysis using a polyclonal antibody. Results: 8/11 mantle cell lymphomas, 0/11 chronic lymphocytic leukemias, 0/4 hairy cell leukemias, 0/2 Sezary syndrome, 0/2 monocytoid B-cell lymphomas, 0/3 follicular lymphomas, and 0/2 reactive hyperplasias had overexpression of cyclin D1. Cytogenetic analysis was performed in four cases of mantle cell lymphoma; three of these cases had the t(11;14), one of which was hypotetraploid with two copies of t(11;14). Immunophenotypically, all cases of mantle cell lymphoma and chronic lymphocytic leukemia had coexpression of CD5 and CD20. Conclusion: Mantle cell lymphoma may be difficult to discriminate from chronic lymphocytic leukemia, a more indolent disease, on morphologic and immunophenotypic grounds. Our findings suggest that analysis of cyclin D1 protein expression may be helpful in differentiating mantle cell lymphomas from other low grade lymphoproliferative disorders.