Molecular targeted therapy for acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease, and the accumulation of various chromosomal and genetic abnormalities is considerably involved in its pathogenesis and prognosis. Recently, the disease classification based on molecular abnormalities and novel molecular-targeting therapies has been developed. In Europe and the United States, several agents have been approved for AML and incorporated into guidelines as the standard treatment depending on comorbid genetic mutations combined with conventional chemotherapy or monotherapy since 2017. The combination therapy of FLT3 inhibitor midostaurin and intensive chemotherapy has improved the prognosis of patients with FLT3-ITD-positive AML, which has been considered a poor prognosis for a long period. In addition to small-molecule compounds, various novel therapies for AML are under clinical investigation, including antibody therapies targeting CD47 and TIM-3, bispecific antibodies, and CAR-T-cell therapies. Considering the treatment strategies with diverse therapeutic modalities, the pathogenesis and clonal selection process of refractory AML, including the surrounding environment of residual leukemia cells, should be clarified. The combination of new therapies and chemotherapies is highly expected to improve the prognosis of patients with AML in the near future.