Immunolocalization of the Bcl-2 protein within hematopoietic neoplasms.
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.
Zutter
M
M
Department of Medicine, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110.
Hockenbery
D
D
Silverman
G A
GA
Korsmeyer
S J
SJ
D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D007945:Leukemia, Lymphoid / Q000378:metabolism; D008198:Lymph Nodes / Q000737:chemistry; D008223:Lymphoma / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000378:metabolism; D008224:Lymphoma, Follicular / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000378:metabolism; D010265:Paraproteinemias / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2
D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2