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 Ba r, are considered to play important roles in the regulation of apoptos is and drug resistance. To understand the significance of these protei ns in fresh human myeloma cells;, expression of Bcl-2 family of protei ns 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 showe d 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 c linical stage while Bcl-X-L tended to be expressed in samples from cas es at advanced clinical stage. Bcl-X-L was significantly expressed in tumor cells from cases with extramedullar lesions. There was no correl ation between the expression levels of Bcl-2 or Bcl-X-L and preceding chemotherapy. Expression of Bar 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 si gnificance in expression of Bcl-2 or Bcl-X-L although Bcl-X-L tended t o be expressed in cases with poor prognosis. These findings indicate t hat expression of Bcl-2 family of proteins is heterogeneously regulate d in fresh myeloma cells. Expression of Bcl-X-L end Bcl-2 may correlat e with extramedullar invasion and early stage of the disease, respecti vely. Absence of Bar in myeloma cells may contribute to low sensitivit y of myeloma cells to anti-cancer agents since Bar is reported to medi ate cytotoxicity of some anti-cancer drugs.