Targeted therapies for high-risk acute myeloid leukemia

Acute myeloid leukemia (AML) is the second most common cause of pediatric leukemia, and approximately 500 children develop AML each year in the United States.(77, 96) Contemporary treatment regimens for AML are unsatisfactory Although most children with AML can achieve initial remissions with intensive chemotherapy, 40% to 60% relapse and eventually succumb to their disease.(37, 11, 119, 138) The related problems of drug resistance and minimal residual disease are the major reasons for the failure of AML therapy. Consequently, the treatment of AML requires the use of high-dose chemotherapy and is accompanied by a high rate of nonspecific toxicity reflected in treatment-related morbidity and mortality The main challenges for the development of effective AML therapies are to identify anticancer agents with novel mechanisms of action that can overcome drug resistance and to develop methods to target effective therapies specifically to clonogenic AML blasts. This article focuses on novel AML-targeted therapies that are being evaluated in early clinical trials (Table 1).