Quantitative analysis detects ubiquitous expression of apoptotic regulators in B cell non-Hodgkin's lymphomas

To determine whether the expression levels of Bcl-2 family apoptotic regulators are correlated with the histopathological heterogeneity of B cell non-Hodgkin's lymphomas (NHL), we quantified their expression in malignant B cell populations isolated from 33 biopsy samples, including small lymphocytic lymphoma (SLL, n = 9), mantle cell lymphoma (MCL, n = 8), follicular lymphoma (FL, n = 8), and diffuse large cell lymphoma (DLCL, n = 8). Normal B cells purified from reactive lymph nodes and tonsil (n = 3) were used as controls. Cell lysates were analyzed by Western blotting, and signals quantified by densitometry. Expression of Bcl-2 and its homologues, Bcl-xL, Bcl-xS, Bax, Bad, Bak and Bag-1, was detected in all NHL cases, with wide variations between histological subtypes and within each subtype. Statistically significant differences were: (1) a higher level of Bad expression in DLCL compared to FL and MCL; (2) a lower level of Bak expression in FL compared to DLCL, SLL and MCL; and (3) a higher Bag-1 expression level in FL compared to SLL. When compared to NHL cells, normal B cells showed a higher level of Bax expression, and a lower level of Bcl-xL expression. Thus, quantitative analysis shows ubiquitous expression of Bcl-2 family proteins in normal and neoplastic B cells; the variations in expression levels may contribute to both the B-NHL clinicopathological diversity and the different apoptotic sensitivities of normal B cells vs B-NHL cells.