Targeted therapeutic approaches for AML

Acute myeloid leukemia comprises about 20% of the acute leukemias in children, but it is responsible for more than half of leukemic deaths due to leukemia. Compared to the tremendous success in the treatment of acute lymphocytic leukemia in the last three decades, resulting in more than 80% cure rate, improvements in AML therapy have been more limited with only about half of patients with AML being cured. Risk-adapted therapy has been the cornerstone of ALL therapy. One of the reasons for the success of this approach in ALL is that standard ALL induction and consolidation have been able to be intensified without causing significant morbidity and mortality. In contrast, the leukemic stem cell in most AML subtypes is inherently more drug resistant requiring significantly intensified courses of near myeloablative combinations of chemotherapeutic agents. This has resulted in a plateau in survival at approximately 50% along with significant morbidity and mortality.