Effect of IDH gene mutation on acute myeloid leukemia / 上海交通大学学报（医学版）

ABSTRACT

Isocitrate dehydrogenase (IDH) is an important metabolic enzyme involved in the tricarboxylic acid cycle. In recent years, IDH has become the most frequent tumor metabolic mutation gene in acute myeloid leukemia (AML). Unlike other mutations, it gains new functions which can catalyze α-ketoglutarate (α-KG) to produce the tumor metabolite D-2-hydroxyglutarate (D-2-HG). The increased D-2-HG in the cells can affect bone marrow cell differentiation and proliferation and induce myeloid tumors by the genetic controls, cell signaling, bone marrow microenvironment changes and other ways. Currently, the new IDH2 inhibitors AG-221 and IDH1 inhibitors become the first-line drugs targeted therapy in patients with IDH mutations in AML. This paper focused on the mutation of IDH and its mutation characteristics, the formation mechanism of AML by the metabolites produced by mutation, the metabolic pathway of tumor metabolites and the research progress of IDH inhibitors.