Detection of apoptosis in acute promyelocytic leukemia cells in vivo during differentiation-induction with all-trans retinoic acid in combination with chemotherapy

In two patients with acute promyelocytic leukemia (APL) treated with all-tr ans retinoic acid (ATRA) in combination with chemotherapy, we demonstrated that cells with apoptotic morphology were recognized in a small fraction of whole blood cells (0.2-0.4%) at the regression phase of leukocytosis with mostly maturing aberrant granulocytes of APL clone origin. Moreover, in a l ight-density cell fraction (< 1.077) of peripheral blood or marrow cells ob tained from three patients, DNA fragmentation was detected by agarose gel e lectrophoresis temporarily. These findings may suggest that, during the tre atment with ATRA, a small fraction of APL cells maturing toward the stage o f terminal differentiation underwent apoptosis in vivo, which might be enri ched by the combination of chemotherapy to ATRA administration. (C) 1999 El sevier Science Ltd. All rights reserved.