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In the past two decades, there has been a tremendous increase in our understanding of the molecular mechanism of human leukemias. Leukemias are now recognized as a deregulated state of cell proliferation, differentiation and apoptosis, which is induced by gene alterations, including chromosomal translocations. Many of the mechanisms are potentially exploited as new targets for drug development. All-trans retinoic acid therapy for acute promyelocytic leukemia, which was initially developed as a differentiation therapy in an experienced-based manner, is currently known to be the first successful oncoprotein-directed therapy. Basic and clinical research into ATRA-resistance provides new directions for acute myeloid leukemia therapy. Anti-leukemia therapy will continue to lead the field of chemotherapy in the coming decades.

Mechanism-based therapy for leukemia: a lesson from ATRA therapy.