Research Progress in the Pharmacogenomics of Agents for Treatment of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults, which is characterized by aggressive biology and poor prognosis.The combined chemotherapy of Ara-C and anthracyclines is the most important treatment regimen for AML.However, 20%-40% of patients failed to achieve complete response after the induction chemotherapy, with primary or acquired drug resistance occurring in most of the patients.Researchers at home and abroad have carried out a series of pharmacogenomics studies on AML, focusing on the influence of genetic mutations in drug metabolism enzymes, drug transporters and drug targets on the efficacy of chemotherapy and prognosis of the disease.With the development and application of sequencing technology, clinical studies have shown that somatic mutations such as those in FLT3, TP53, and PML-RARα are associated with the pathogenesis and prognosis of AML.As a targeted therapy against PML-RARα fusion gene, As₂O₃ has been widely used for the treatment of M3 subtype of AML with satisfied efficacy.New drugs targeting FLT3 have been under intensive investigation, among which midostaurin and gilteritinib have been approved by FDA for the treatment of FLT3 mutation-positive AML patients.In this paper, the advancement in pharmacogenomics of agents for treatment of AML was reviewed from the aspects of mutations in drug transporters and metabolizers, mutations in molecular targets and AML somatic mutations, so as to provide more information for the AML individualized therapy.