Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells.

摘要: Objective Antiapoptotic Bcl-2 is overexpressed in most cases of chronic lymphocytic leukemia (CLL). The inhibition the antiapoptotic proteins an attractive strategy for either restoring normal apoptotic process cancer cells or making these more susceptible to conventional chemotherapy. We studied effect inhibitors on viability from CLL and other mature B-cell neoplasms. Materials Methods cytotoxic effects four nonpeptidic cell-permeable (HA14-1, antimycin A, GX15-003, GX15-070) B patients with CLL, mantle cell lymphoma (MCL), splenic marginal zone (SMZL). Moreover, we analyzed combination fludarabine chlorambucil. Results HA14-1 induced apoptosis EC 50 lower than μM 26 36 samples analyzed. mean sensitive was 23 ± 2 μM. Antimycin A 13 18 Both cytochrome c release mitochondria caspase-3 activation. peripheral MCL SMZL. also alterations p53 ATM. Finally, GX compounds 9 11 tested. HA14-1, chlorambucil had additive cells. Conclusion induce ex vivo could be used as monotherapy given current