Proliferation and apoptosis in newly diagnosed and relapsed childhood acute lymphoblastic leukemia

Children with acute lymphoblastic leukemia (ALL) who are treated with chemo therapy have remissions in more than 95% of the cases. However, 25% of the patients relapse and show resistance to chemotherapy. In this investigation we compared 25 newly diagnosed and 25 relapsed cases of ALL with respect t o proliferation and apoptosis. Using immunocytochemistry and Western blotti ng, we determined the expression of cyclin A protein as a measure of the pr oliferative activity and the pro-apoptotic and anti-apoptotic factors, Fas, Fas ligand, caspase-3 and Bcl-2. Cyclin A expression was observed in 32% o f the newly diagnosed cases and in 52% of the relapsed cases. Expression of Fas was found in 58% of the the newly diagnosed and in only 27% of the I e lapsed samples. Of the newly diagnosed ALL, 88% expressed the Fas ligand wh ile such expression was observed in 54% of the relapsed ALL. Sixty-four per cent of the newly diagnosed cases expressed caspase-3 while only 48% of the relapsed samples did so. The anti-apoptotic factor, Bcl-2, was ;more frequ ently expressed in relapsed than in newly diagnosed cases. These data indic ate that relapsed ALL more frequently exhibits high proliferative activity and reduced apoptosis than does newly diagnosed ALL.