Expression of BAX in plasma cell dyscrasias

Several studies demonstrate that the BCL-2 and BCL-XL antiapoptotic genes a re variably expressed in plasma cells of patients with multiple myeloma (MM ). However, the plasma cell expression of BAX protein, their major proapopt otic partner, has not been investigated. Our initial Western blot analysis of myeloma cell extracts also suggested patient variability in the expressi on of BAX, which was not altered by exposure to interleukin 6, To further I nvestigate the significance of BAX expression, we performed immunohistochem istry on archival bone marrow biopsies and compared BAX staining to BCL-2 i mmunostaining. Expression was first evaluated in 104 patients with reactive plasmacytosis, monoclonal gammopathy of undetermined significance/smolderi ng MM, or active RIM. An increase (P < 0.05) in expression of both BAX and BCL-2 was detected in MM patients compared with patients with reactive plas macytosis, Patients with monoclonal gammopathy of undetermined significance /smoldering MM had intermediate values. For correlations with outcome, expr ession was assessed in 43 patients at diagnosis who were treated with melph alan and prednisone; 30 at diagnosis who were treated with vincristine, Adr iamycin, and dexamethasone; and 29 at relapse who were treated with second- line therapy. There was no correlation between PAX or BCL-2 expression and response to chemotherapy or duration of response or between BCL-2 expressio n and survival, However, patients who demonstrated extremely low plasma cel l BAX expression had significantly increased survival. This was true for pa tients initially treated with melphalan and prednisone or vincristine, Adri amycin, and dexamethasone, as well as patients studied at relapse. BAX expr ession did not correlate with expression of proliferating cell nuclear anti gen used as a marker of proliferation. These data indicate a myeloma-specif ic increase in BAX expression in plasma cells and suggest that low PAX expr ession identifies a cohort of patients with long survival, which is not spe cifically associated with low proliferating cell nuclear antigen expression .