Tallman M S
Leukemia Program, Robert H. Lurie Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Leukemia. 1996 Apr;10 Suppl 1:S12-5.
The standard treatment of patients with acute myeloid leukemia (AML) has depended on the elimination of the leukemic clone with cytotoxic myeloablation. Differentiation therapy is receiving increasing attention due to the remarkable activity of a vitamin A derivative, all-trans retinoic acid (ATRA), in patients with acute promyelocytic leukemia (APL). The majority of patients treated have achieved complete remission and with rapid resolution of the life-threatening bleeding diathesis. Phase II studies with ATRA in APL indicate certain limitations in the therapeutic use of retinoic acid. Patients achieving complete remission with ATRA alone require postremission chemotherapy, once remission is achieved, to extend remission. The results of differentiating therapy in APL patients has encouraged the use of differentiating therapy in patients with non-M3 AML. A number of areas await research, such as the need to develop ways to overcome acquired retinoic resistance and the development of cytochrome P450 inhibitors. Other novel retinoids, such as 9-cis-retinoic acid, may be even more effective than ATRA in APL. Additional important areas of research involve studying combinations of retinoids and other putative differentiating agents, and identifying different selected treatments targeted at specific molecular defects.
急性髓系白血病（AML）患者的标准治疗依赖于通过细胞毒性骨髓清除来消除白血病克隆。由于维生素A衍生物全反式维甲酸（ATRA）在急性早幼粒细胞白血病（APL）患者中具有显著活性，分化疗法正受到越来越多的关注。大多数接受治疗的患者已实现完全缓解，危及生命的出血素质也迅速得到缓解。在APL中使用ATRA的II期研究表明维甲酸在治疗应用中有一定局限性。仅用ATRA实现完全缓解的患者在缓解后需要进行缓解后化疗以延长缓解期。APL患者分化疗法的结果促使在非M3 AML患者中使用分化疗法。还有许多领域有待研究，例如需要开发克服获得性维甲酸耐药性的方法以及细胞色素P450抑制剂的研发。其他新型维甲酸，如9-顺式维甲酸，在APL中可能比ATRA更有效。其他重要的研究领域包括研究维甲酸与其他假定分化剂的联合使用，以及确定针对特定分子缺陷的不同选择治疗方法。
