Current Understandings of Myeloid Differentiation Inducers in Leukemia Therapy

Differentiation therapy using all-trans retinoic acid for acute promyelocytic leukemia (APL) is well established. Several attempts have been made to treat non-APL, AML patients by employing differentiation inducers, such as hypomethylating agents (HMAs), and low-dose cytarabine (Ara-C) (LDAC), with encouraging results. Other than HMAs and LDAC, various inducers of myeloid cell differentiation have been identified. This review describes and categorizes these inducers, which include glycosylation modifiers, epigenetic modifiers, vitamin derivatives, cytokines, and chemotherapeutic agents. Some of these inducers are currently being used in clinical trials. I highlight the potential applications of glycosylation modifiers and epigenetic modifiers, which are attracting increasing attention in their use as differentiation therapy against AML. Among the agents described in this review, epigenomic modifiers seem particularly promising, and particular attention should also be paid to glycosylation modifiers. These drugs may signal a new era for AML differentiation therapy.