Proliferation and apoptosis in newly diagnosed and relapsed childhood acute lymphoblastic leukemia.
Children with acute lymphoblastic leukemia (ALL) who are treated with chemotherapy 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 to proliferation and apoptosis. Using immunocytochemistry and Western blotting, we determined the expression of cyclin A protein as a measure of the proliferative activity and the pro-apoptotic and anti-apoptotic factors, Fas, Fas ligand, caspase-3 and Bcl-2. Cyclin A expression was observed in 32% of the newly diagnosed cases and in 52% of the relapsed cases. Expression of Fas was found in 58% of the newly diagnosed and in only 27% of the relapsed samples. Of the newly diagnosed ALL, 88% expressed the Fas ligand while such expression was observed in 54% of the relapsed ALL. Sixty-four percent 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 frequently expressed in relapsed than in newly diagnosed cases. These data indicate that relapsed ALL more frequently exhibits high proliferative activity and reduced apoptosis than does newly diagnosed ALL.
Volm
M
M
German Cancer Research Center, Department of Oncological Diagnostics and Therapy, Heidelberg, Germany.
Zintl
F
F
Sauerbrey
A
A
Koomägi
R
R
D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D002455:Cell Division; D002648:Child; D019925:Cyclin A / Q000096:biosynthesis; D053222:Fas Ligand Protein; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012008:Recurrence; D019014:fas Receptor / Q000096:biosynthesis*
D019925:Cyclin A; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases