Division of Laboratory Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan,
Acta Haematol. 2021;144(4):380-388. doi: 10.1159/000510980. Epub 2020 Nov 20.
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.
全反式维甲酸诱导分化治疗急性早幼粒细胞白血病(APL)已得到广泛认可。目前已有多项尝试采用分化诱导剂(如低甲基化药物(HMAs)和低剂量阿糖胞苷(Ara-C)(LDAC))治疗非 APL、急性髓细胞白血病(AML)患者,取得了令人鼓舞的结果。除 HMAs 和 LDAC 外,还发现了多种诱导髓系细胞分化的诱导剂。本综述对这些诱导剂进行了描述和分类,包括糖基化修饰剂、表观遗传修饰剂、维生素衍生物、细胞因子和化疗药物。其中一些诱导剂目前正在临床试验中使用。我强调了糖基化修饰剂和表观遗传修饰剂的潜在应用,它们在作为 AML 分化治疗方面的应用越来越受到关注。在本综述中描述的药物中,表观遗传修饰剂似乎特别有前途,应特别注意糖基化修饰剂。这些药物可能为 AML 分化治疗带来新的时代。