Arsenic and apoptosis in the treatment of acute promyelocytic leukemia

Remarkable progress has been made in identifying the onco-genic fusion proteins that are produced as a result of specific chromosomal translocations in the human acute leukemias (1). Because these proteins are expressed only by cells within the leukemic clones, they hold great promise as targets for new drugs that will specifically destroy leukemic cells while leaving normal cells unharmed. Both all-trans-retinoic acid (t-RA) and arsenic trioxide (As2O3) have shown this type of activity in patients with acute promyelocytic leukemia (APL) whose blast cells harbor the t(15;17) chromosomal translocation and express the PML/RARa fusion protein. Each of these agents was iden-tified empirically in innovative clinical trials conducted by in-vestigators at the Shanghai and Harbin Institutes of Hematology in China (2,3). A plausible biochemical basis for the selective action of t-RA became apparent once the PML/RARa fusio