Differentiation therapy of leukemia: achievements, limitations and future prospects.

Differentiation therapy in patients with acute promyelocytic leukemia (APL) using all-trans-retinoic acid (ATRA) has now been established as an effective strategy for the treatment of leukemia. However, the clinical response of patients with leukemias other than APL to differentiation inducers is limited, often with inconsistent outcome. Recently, numerous new differentiation inducers for various leukemia cells have been developed, some of which have had therapeutic effects on various leukemias in preclinical and clinical trials. Additionally, molecular control mechanisms of differentiation, and apoptosis of various leukemia cells by differentiation inducers have been studied extensively. These studies suggest that problems underlying the current discrepancy between preclinical and clinical therapeutic efficacy of leukemias can be overcome by these basic studies together with multidisciplinary studies on the therapy of leukemias in combination with differentiation therapy and other conventional therapies.