Jing Y, Waxman S
Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1178, New York, NY 10029-6547, USA.
Curr Top Microbiol Immunol. 2007;313:245-69. doi: 10.1007/978-3-540-34594-7_13.
Acute promyelocytic leukemia (APL) is an unique subtype of acute myeloid leukemia typically carrying a specific reciprocal chromosome translocation, t(15;17), leading to the expression of a leukemia-generating fusion protein, PML-RARalpha. APL patients are responsive to APL-selective reagents such as all-trans retinoic acid (ATRA) or arsenic trioxide and non-selective cytotoxic chemotherapy. Nearly all de novo APL patients undergo clinical remission when treated with ATRA plus chemotherapy or with the combinational selective therapy, ATRA plus As2O3. Combining ATRA with As2O3 as an induction followed by chemotherapy consolidation results in more profound clinical remissions compared to treatment with any agent alone or any of the other possible combinations. The mechanism of action of each of these agents differs. ATRA induces APL cell differentiation and PML-RARalpha proteolysis. As2O3 induces APL cell partial differentiation, PML-RARalpha proteolysis, and apoptosis. Chemotherapy, mainly using anthracyclines, induces APL cell death. The combined effects of selective APL therapy (ATRA and As2O3) and/or non-selective chemotherapy in APL cells in vitro and their mechanisms in relation to clinical protocol design are discussed.
急性早幼粒细胞白血病（APL）是急性髓系白血病的一种独特亚型，通常携带特定的相互易位染色体，t(15;17)，导致产生白血病的融合蛋白PML-RARα的表达。APL患者对APL选择性试剂如全反式维甲酸（ATRA）或三氧化二砷以及非选择性细胞毒性化疗有反应。几乎所有初发APL患者在接受ATRA加化疗或联合选择性治疗（ATRA加As2O3）时都会出现临床缓解。与单独使用任何一种药物或任何其他可能的组合治疗相比，将ATRA与As2O3联合作为诱导治疗，随后进行化疗巩固，可导致更深度的临床缓解。这些药物各自的作用机制不同。ATRA诱导APL细胞分化和PML-RARα蛋白水解。As2O3诱导APL细胞部分分化、PML-RARα蛋白水解和凋亡。化疗主要使用蒽环类药物，诱导APL细胞死亡。本文讨论了选择性APL治疗（ATRA和As2O）和/或非选择性化疗在体外对APL细胞的联合作用及其与临床方案设计相关的机制。
