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.