Varghese L, Janckila A, Yam L T
Department of Medicine, University of Louisville, KY, USA.
J Ky Med Assoc. 1999 Feb;97(2):61-5.
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by hypergranular leukemic cells, bleeding diathesis and t(15; 17) translocation. The t(15; 17) translocation leads to the production of the PML-RAR alpha fusion protein which plays a vital role in the pathogenesis of APL by arresting normal differentiation of myeloid precursors. However, in the presence of high concentrations of all-trans-retinoic acid (ATRA), the PML-RAR alpha fusion protein serves to stimulate cell differentiation. The diagnosis of APL and the detection of residual disease are based on the t(15; 17) translocation. Treatment with a combination of ATRA and anthracycline-AraC chemotherapy has shown a higher rate of complete remission in APL. We report the case of a 71-year-old male with the rare microgranular variant of APL to illustrate these findings. The patient was treated with a combination of ATRA and Daunorubicin-AraC chemotherapy and achieved complete remission. He developed retinoic acid syndrome as a complication of therapy with ATRA. The methods for diagnosis, the molecular mechanisms in the oncogenesis of APL, rationale of treatment of APL with ATRA, complications of therapy and the new concepts in the treatment of ATRA-resistant APL 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，其特征为白血病细胞颗粒增多、出血倾向以及t(15; 17)易位。t(15; 17)易位导致PML-RARα融合蛋白的产生，该蛋白通过阻止髓系前体细胞的正常分化在APL发病机制中起关键作用。然而，在高浓度全反式维甲酸（ATRA）存在的情况下，PML-RARα融合蛋白可促进细胞分化。APL的诊断和残留疾病的检测基于t(15; 17)易位。ATRA与蒽环类-阿糖胞苷化疗联合治疗已显示出APL更高的完全缓解率。我们报告一例71岁男性APL罕见微颗粒变异型病例以阐述这些发现。该患者接受ATRA与柔红霉素-阿糖胞苷化疗联合治疗并实现完全缓解。他发生了维甲酸综合征，这是ATRA治疗的一种并发症。本文讨论了APL的诊断方法、APL肿瘤发生的分子机制、ATRA治疗APL的理论基础、治疗并发症以及耐ATRA的APL治疗的新概念。
