Elsevier

Human Pathology

Volume 35, Issue 9, September 2004, Pages 1095-1100
Human Pathology

Original contributions
MCL-1 expression in B-cell non-Hodgkin’s lymphomas

https://doi.org/10.1016/j.humpath.2004.04.018Get rights and content

Abstract

B-cell non-Hodgkin’s lymphomas are known to express BCL-2 family proteins, of which the myeloid cell leukemia-1 (MCL-1) protein is a member. MCL-1 is involved in viability and immortalization of normal and neoplastic B cells, and expression is regulated transcriptionally and posttranscriptionally, resulting in an anti-apoptotic (full length) or a pro-apoptotic (short isoform) gene product. In this study, we assessed 151 B-cell lymphomas for MCL-1 expression and analyzed for expression of the full-length and short isoforms of MCL-1 in B-cell lymphoma cell lines. By using immunohistochemistry, a subset of neoplasms in 9 lymphoma types studied expressed MCL-1, but expression was more frequent and intense in high-grade (43 of 49, 88%) compared with low-grade (34 of 92, 37%) lymphomas (P < 0.0001). In follicular lymphomas, MCL-1 expression positively correlated with increasing grade; 1 (14%) of eight grade 1, 7 (70%) of ten grade 2, and all 9 (100%) grade 3 were positive (P < 0.0008). All plasma cell myeloma cases assessed were also MCL-1 positive. By using Western blot analysis, 6 of 7 high-grade B-cell lymphoma cell lines showed predominant expression of full-length MCL-1, compared with no or weak expression of the short isoform. One myeloma and 1 of 2 mantle cell lymphoma cell lines also tested showed only full-length isoform expression. Our data suggest that MCL-1 is frequently expressed in high-grade B-cell lymphomas and plasma cell myeloma, most likely in its full-length isoform that is an active anti-apoptotic gene product. MCL-1 expression also correlates with grade and may contribute to transformation in follicular lymphomas.

Section snippets

B-cell non-Hodgkin’s lymphomas

The study group included 151 B-cell lymphomas accessioned at The University of Texas M. D. Anderson Cancer Center between 1981 and 2000. The diagnosis of these tumors was based on morphological and immunohistological criteria according to the World Health Organization (WHO) classification.21 The study group included 38 cases of mantle cell lymphoma, 31 diffuse large B-cell lymphoma, 27 follicular lymphoma (eight grade 1, ten grade 2, nine grade 3), 14 small lymphocytic lymphoma/chronic

MCL-1 protein expression in B-cell lymphomas

Among low-grade B-cell neoplasms, MCL-1 was expressed in 4 of 5 (80%) nodal and splenic marginal zone B-cell lymphoma, 4 of 11 (36%) extranodal marginal zone B-cell lymphoma of MALT type, 13 of 38 (34%) mantle cell lymphoma, 4 of 14 (29%) small lymphocytic lymphoma/chronic lymphocytic leukemia, and 1 of 6 (17%) lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (Table 1; Fig 1). The staining intensity of MCL-1 in these tumors was weak, with relatively low percentages (10%-50%) of

Discussion

In this study, we analyzed MCL-1 expression in a series of low- and high-grade B-cell non-Hodgkin’s lymphomas of various types. MCL-1 was more frequently expressed in high-grade (88%) compared with low-grade (37%) lymphomas (P < 0.0001). In addition, MCL-1 expression was present in a significantly higher proportion of cells and was of stronger intensity in high-grade compared with low-grade B-cell lymphomas. These findings agree with 3 other studies that detected MCL-1 in high-grade B-cell

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