MAL expression in lymphoid cells: further evidence for MAL as a distinct molecular marker of primary mediastinal large B-cell lymphomas.
The MAL mRNA was initially identified during T-cell development and was later found in myelin-forming cells and certain polarized epithelial cell lines. It encodes a proteolipid believed to participate in membrane microdomains stabilization, transport machinery and signal transduction. Using a differential display reverse-transcription approach, we identified MAL as a distinct molecular marker of primary mediastinal large B-cell lymphoma compared with nonmediastinal diffuse large B-cell lymphomas. In the present study, we used immunohistochemistry to extend MAL expression analysis to normal lymphoid tissues; to 185 lymphomas representing most B, T, and Hodgkin lymphoma entities; and to the primary mediastinal large B-cell lymphoma derived B-cell line MedB-1. In addition, B and T cells from peripheral blood, tonsil, and spleen were analyzed by flow cytometry. Our results show that MAL is highly expressed in thymocytes, in a large percentage of peripheral CD4 T cells, and in a lower proportion of CD8 peripheral T cells. In the normal B-cell compartment, MAL expression appears to be restricted to a minor subpopulation of thymic medullary B cells and to occasional mature plasma cells located in the interfollicular areas of tonsil and lymph nodes. Among B-cell lymphomas (n = 110), MAL expression in tumor cells was observed in 21/33 primary mediastinal large B-cell lymphomas (70%) and in 3/5 plasmacytoma/myeloma, but not in all other B-cell lymphomas with the exception of 1/33 nonmediastinal diffuse large B-cell lymphomas. The MedB-1 B-cell line was also MAL positive. Among T-cell neoplasms, MAL was highly expressed in lymphoblastic tumors (5/6), whereas mature T-cell lymphomas were essentially MAL negative (27/28). Among 41 Hodgkin lymphomas, 3 nodular-sclerosing cases with mediastinal involvement showed MAL-positive Reed Sternberg cells. In conclusion, this study further supports thymic B cells as the putative normal counterpart of primary mediastinal large B-cell lymphomas and supports MAL as a distinct molecular marker of this lymphoma subtype among diffuse large B-cell lymphomas.
Copie-Bergman
Christiane
C
Département de Pathologie, Service d'Immunologie Biologique, Service d'Hématologie Clinique, Hôpital Henri Mondor, Créteil, France.
Plonquet
Anne
A
Alonso
Miguel A
MA
Boulland
Marie-Laure
ML
Marquet
Jeanine
J
Divine
Marine
M
Möller
Peter
P
Leroy
Karen
K
Gaulard
Philippe
P
D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D051925:CD79 Antigens; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology; D008214:Lymphocytes / Q000737:chemistry; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology*; D008479:Mediastinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D026901:Membrane Transport Proteins; D009185:Myelin Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D014066:Palatine Tonsil / Q000737:chemistry / Q000473:pathology; D011510:Proteolipids / Q000096:biosynthesis*; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D013154:Spleen / Q000737:chemistry / Q000473:pathology; D013950:Thymus Gland / Q000737:chemistry / Q000473:pathology
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051925:CD79 Antigens; C497881:CD79A protein, human; C569026:MAL protein, human; D026901:Membrane Transport Proteins; D009185:Myelin Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D011510:Proteolipids; D011947:Receptors, Antigen, B-Cell