title: Expression of Smac/DIABLO in B-cell non-Hodgkin and Hodgkin lymphomas.
abstract: Inhibitor of apoptosis proteins (IAPs) are upregulated in cancers and suppress cell death, in part, through their ability to directly inhibit caspases. Inhibitor of apoptosis proteins are differentially expressed in B-cell lymphomas. The functions of some IAPs are counteracted by the cell death inducer, second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO). In this study, we investigated the expression levels of Smac/DIABLO in 14 lymphoma cell lines by Western blot analysis. We also assessed 247 B-cell non-Hodgkin's lymphoma (NHL) and 40 Hodgkin's lymphoma (HL) tumors using immunohistochemical methods. Smac/DIABLO was expressed in most NHL and all HL cell lines. In NHL, Smac/DIABLO was expressed in 117 (47%) tumors and was differentially expressed in various NHL types. In most NHLs, from 29% to 68% of tumors were positive; however, Smac/DIABLO was not detected in small lymphocytic lymphoma/chronic lymphocytic leukemia and Burkitt lymphoma, and was rare in extranodal marginal zone B-cell lymphoma. In HL, Smac/DIABLO was positive in 25 (63%) tumors. Unlike NHL, all types of HL were positive for Smac/DIABLO, although nodular sclerosis was least often positive. The differential expression of Smac/DIABLO in NHLs suggests that apoptotic mechanisms are differentially involved in their pathogenesis. These results may also have implications for using Smac/DIABLO or its agonists as therapeutic agents.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Ren
authors.forename: Nalan
authors.initials: N
authors.lastname: Akyurek
authors.forename: Ellen
authors.initials: E
authors.lastname: Schlette
authors.forename: Georgios Z
authors.initials: GZ
authors.lastname: Rassidakis
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
mesh_terms: D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015870:Gene Expression; D006689:Hodgkin Disease / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*
chemical_list: D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins