Beneficial and Adverse Effects of Molecularly Targeted Therapies for Acute Promyelocytic Leukemia in Central Nervous System
Beneficial and Adverse Effects of Molecularly Targeted Therapies for Acute Promyelocytic Leukemia in Central Nervous System
复制标题
DOI：
10.2174/187152709789541943
复制
发表时间：
2009-11-01
影响因子：
3
通讯作者：
Kurokawa, Mineo
中科院分区：
文献类型：
--
作者：
Nagai, Sumimasa;Takahashi, Tsuyoshi;Kurokawa, Mineo
急性早幼粒细胞白血病(APL)是急性髓系白血病的一个独特亚型，其特征是一种异常的融合蛋白PML/RARA。全反式维甲酸(ATRA)和三氧化二砷是APL的主要分子靶向治疗药物，它们影响或降解PML/RARA融合蛋白，导致APL细胞分化和凋亡。这些疗法改善了APL患者的预后，现在是APL的主要治疗选择。此外，getuzumab ozogamicin是APL的另一种靶向治疗。另一方面，APL中枢神经系统(CNS)复发患者预后较差。因此，中枢神经系统复发已成为人们关注的主要问题，需要对中枢神经系统复发采取有效的治疗方法。事实上，分子靶向治疗在APL中枢神经系统复发中可能的积极作用已被提出，并已在APL中研究了几种分子靶向治疗中枢神经系统复发的新方法。在这篇综述中，我们讨论了三个主要主题：APL分子靶向治疗的引入与中枢神经系统复发之间的关系，APL中枢神经系统复发靶向治疗的新途径，以及靶向治疗的其他并发症，如全反式维甲酸诱发的大脑假瘤和蛛网膜下腔出血。这种全面的认识将有助于更好地管理APL患者。
Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia characterized by an abnormal fusion protein, PML/RARA. All-trans retinoic acid (ATRA) and arsenic trioxide, which are the major molecularly targeted therapies in APL, affect or degrade the PML/RARA fusion protein and cause differentiation and apoptosis of APL cells. These therapies have improved the prognosis of APL patients and are now the main therapeutic options in APL. In addition, gemtuzumab ozogamicin is another targeted therapy in APL. On the other hand, the prognosis of patients with central nervous system (CNS) relapses of APL remains poor. Therefore, CNS relapses have become major concerns, and effective therapeutic approaches for CNS relapses are needed. In fact, possible active roles of molecularly targeted therapies in CNS relapses of APL have been suggested, and several new approaches with molecularly targeted therapies for CNS relapses have been examined in APL. In this review, we discuss three main topics; the relationship between the incidence of CNS relapses and the introduction of molecularly targeted therapies for APL, new approaches with targeted therapies for CNS relapses of APL, and other complications of targeted therapies in CNS such as pseudotumor cerebri induced by ATRA and subarachnoid hemorrhage. This comprehensive understanding would be helpful for better management of patients with APL.