Expression of Bcl-2 family of proteins in fresh myeloma cells

Members of the Bcl-2 family of proteins, Bcl-2, Bcl-X-L, Bcl-Xs and Bax, are considered to play important roles in the regulation of apoptosis and drug resistance. To understand the significance of these proteins in fresh human myeloma cells;, expression of Bcl-2 family of proteins was analyzed by Western blotting in 17 cases with multiple myeloma (MM) and three cases with plasma cell leukemia (PCL). Bcl-2 and Bcl-X-L were found in 12 and nine samples, respectively. All PCL cases showed co-expression of Bcl-2 and Bcl-X-L. Analysis of MM cases showed that Bcl-2 was preferentially expressed in samples from cases with early clinical stage while Bcl-X-L tended to be expressed in samples from cases at advanced clinical stage. Bcl-X-L was significantly expressed in tumor cells from cases with extramedullar lesions. There was no correlation between the expression levels of Bcl-2 or Bcl-X-L and preceding chemotherapy. Expression of Bax was found in only one patient who had pleural effusion caused by invasion of myeloma cells and a high serum LDH level. Survival analysis revealed that there was no statistical significance in expression of Bcl-2 or Bcl-X-L although Bcl-X-L tended to be expressed in cases with poor prognosis. These findings indicate that expression of Bcl-2 family of proteins is heterogeneously regulated in fresh myeloma cells. Expression of Bcl-X-L end Bcl-2 may correlate with extramedullar invasion and early stage of the disease, respectively. Absence of Bax in myeloma cells may contribute to low sensitivity of myeloma cells to anti-cancer agents since Bax is reported to mediate cytotoxicity of some anti-cancer drugs.