Copie-Bergman Christiane, Plonquet Anne, Alonso Miguel A, Boulland Marie-Laure, Marquet Jeanine, Divine Marine, Möller Peter, Leroy Karen, Gaulard Philippe
Département de Pathologie, Service d'Immunologie Biologique, Service d'Hématologie Clinique, Hôpital Henri Mondor, Créteil, France.
Mod Pathol. 2002 Nov;15(11):1172-80. doi: 10.1097/01.MP.0000032534.81894.B3.
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.
MAL信使核糖核酸最初是在T细胞发育过程中被鉴定出来的，后来在形成髓鞘的细胞和某些极化上皮细胞系中被发现。它编码一种蛋白脂质，据信参与膜微结构域的稳定、运输机制和信号转导。使用差异显示逆转录方法，我们确定MAL是原发性纵隔大B细胞淋巴瘤与非纵隔弥漫性大B细胞淋巴瘤相比的一种独特分子标志物。在本研究中，我们使用免疫组织化学将MAL表达分析扩展至正常淋巴组织；185例代表大多数B、T和霍奇金淋巴瘤实体的淋巴瘤；以及原发性纵隔大B细胞淋巴瘤衍生的B细胞系MedB-1。此外，通过流式细胞术分析外周血、扁桃体和脾脏中的B细胞和T细胞。我们的结果表明，MAL在胸腺细胞、大部分外周CD4 T细胞以及较低比例的CD8外周T细胞中高表达。在正常B细胞区室中，MAL表达似乎仅限于胸腺髓质B细胞的一个小亚群以及位于扁桃体和淋巴结滤泡间区域的偶尔成熟浆细胞。在B细胞淋巴瘤（n = 110）中，在21/33例原发性纵隔大B细胞淋巴瘤（70%）和3/5例浆细胞瘤/骨髓瘤的肿瘤细胞中观察到MAL表达，但在所有其他B细胞淋巴瘤中未观察到，1/33例非纵隔弥漫性大B细胞淋巴瘤除外。MedB-1 B细胞系也是MAL阳性。在T细胞肿瘤中，MAL在淋巴母细胞瘤中高表达（5/6），而成熟T细胞淋巴瘤基本上是MAL阴性（27/28）。在41例霍奇金淋巴瘤中，3例有纵隔受累的结节硬化型病例显示MAL阳性的里德·斯腾伯格细胞。总之，本研究进一步支持胸腺B细胞作为原发性纵隔大B细胞淋巴瘤假定的正常对应物，并支持MAL作为弥漫性大B细胞淋巴瘤中这种淋巴瘤亚型的独特分子标志物。
