INDUCTION OF APOPTOSIS IN CHILDHOOD ACUTE-LEUKEMIA BY CHEMOTHERAPEUTIC-AGENTS - FAILURE TO DETECT EVIDENCE OF APOPTOSIS IN-VIVO

This study is designed to investigate whether apoptosis occurs in vivo in pediatric patients with acute leukemia during induction therapy. W hen patients with common acute lymphoblastic leukemia (cALL) and acute myeloblastic leukemia (AML) were treated with prednisolone (60 mg/m(2 )/day, p.o. or i.v.) and etoposide (150 mg/m(2)/day, i.v.), respective ly, the blast cell counts fell to below 30% and 5%, respectively, in 1 week. However, during this cytoreduction phase, neither morphological ly apoptotic cells nor fragmentation of DNA derived from peripheral bl ast cells were detected at any preparations. On the other hand, cALL b ut not AML cells spontaneously undergo apoptosis following their cultu re in vitro. The addition of autologous serum instead of fetal calf se rum substantially prevented apoptosis from occurring spontaneously in cALL cells. When cALL and AML cells freshly obtained from patients bef ore therapy were treated in vitro with 10 mu mol/l prednisolone and 20 mu g/ml etoposide, respectively, these cells underwent apoptosis with in 6 hours, as determined by a morphological and DNA fragmentation ass ay. These in vivo and in vitro findings suggest that, although antican cer drugs may induce apoptosis in vivo, these apoptotic cells cannot b e detected due to their rapid removal from the circulation.