Zutter M, Hockenbery D, Silverman G A, Korsmeyer S J
Department of Medicine, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110.
Blood. 1991 Aug 15;78(4):1062-8.
The Bcl-2 proto-oncogene was discovered at the t(14;18) breakpoint found in most follicular B-cell lymphomas and some diffuse large-cell lymphomas. Bcl-2 is unique among proto-oncogenes, being localized to mitochondria and extending cell survival by blocking programmed cell death. We examined Bcl-2 protein expression in 82 hematologic malignancies and reactive lymphoid processes. All lymphomas with Bcl-2 rearrangement demonstrated high levels of Bcl-2 protein. However, most follicular and diffuse lymphomas without Bcl-2 rearrangement also displayed intense Bcl-2 staining. In these cases, mechanisms other than classic translocation may be deregulation Bcl-2. The pattern of Bcl-2 staining in follicular lymphoma is the inverse of the pattern in reactive hyperplasia, confirming a role for Bcl-2 immunolocalization in routine diagnosis. Small lymphocytic malignancies, including small lymphocytic lymphoma, mantle zone lymphoma, and chronic lymphocytic leukemia, expressed intermediate levels of Bcl-2. Bcl-2 protein varied in plasma cell dyscrasias. Bcl-2 protein levels in T-cell lymphomas reflected their corresponding stage of development. No substantial Bcl-2 was present in the Reed-Sternberg cells of nodular sclerosing Hodgkin's disease. Chronic myelogenous leukemia was strongly positive for Bcl-2, consistent with the presence of Bcl-2 in normal myeloid progenitors. Immunohistochemistry identified an expanded spectrum of hematopoietic neoplasms in which Bcl-2 may provide a cell survival advantage.
Bcl-2原癌基因是在大多数滤泡性B细胞淋巴瘤和一些弥漫性大细胞淋巴瘤中发现的t(14;18)断点处被发现的。Bcl-2在原癌基因中是独特的，它定位于线粒体，并通过阻断程序性细胞死亡来延长细胞存活。我们检测了82例血液系统恶性肿瘤和反应性淋巴样病变中的Bcl-2蛋白表达。所有具有Bcl-2重排的淋巴瘤均显示高水平的Bcl-2蛋白。然而，大多数没有Bcl-2重排的滤泡性和弥漫性淋巴瘤也显示出强烈的Bcl-2染色。在这些病例中，除了经典易位之外的机制可能导致Bcl-2失调。滤泡性淋巴瘤中Bcl-2染色模式与反应性增生中的模式相反，这证实了Bcl-2免疫定位在常规诊断中的作用。小淋巴细胞恶性肿瘤，包括小淋巴细胞淋巴瘤、套细胞淋巴瘤和慢性淋巴细胞白血病，表达中等水平的Bcl-2。Bcl-2蛋白在浆细胞发育异常中有所不同。T细胞淋巴瘤中的Bcl-2蛋白水平反映了它们相应的发育阶段。结节硬化型霍奇金病的里-施细胞中不存在大量Bcl-2。慢性粒细胞白血病Bcl-2呈强阳性，这与正常髓系祖细胞中存在Bcl-2一致。免疫组织化学鉴定出一系列扩大的造血肿瘤，其中Bcl-2可能提供细胞存活优势。
