Differentiation therapy in acute myelogenous leukemia (non-APL)
Differentiation therapy in acute myelogenous leukemia (non-APL)
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DOI：
10.1038/sj.leu.2401714
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发表时间：
2000-03
期刊：
影响因子：
11.4
通讯作者：
S. Waxman
中科院分区：
文献类型：
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作者：
S. Waxman
急性早幼粒细胞白血病 (APL) 的成功治疗已经确定了几种诱导白血病细胞分化和选择性凋亡的新方法，通过克服 APL 和其他形式的急性粒细胞白血病 (AML) 特征的显性融合白血病蛋白的位点特异性转录抑制。这些治疗方法包括使用位点特异性配体、受体和细胞因子、破坏显性融合致白血病蛋白、染色质重塑以及将上述方法与细胞毒性化疗相结合。除细胞毒性化疗外，上述治疗策略不会显着影响正常造血功能，并且它们的组合已被证明在诱导几种 AML 细胞系和 APL 患者的骨髓分化和细胞凋亡方面具有协同作用。一般来说，这些方法不存在交叉耐药性，并且应该具有良好的耐受性，特别是对于老年 AML 患者。目前正在开展包括分化诱导、组蛋白乙酰化和选择性细胞凋亡的生物学终点在内的临床研究，以评估这些治疗 AML 的策略。
Successful treatment of acute promyelocytic leukemia (APL) has identified several novel approaches to induce leukemic cell differentiation and selective apoptosis by overcoming the site-specific transcriptional repression by dominant fusion leukemogenic proteins characteristic of APL and other forms of acute myelogenous leukemia (AML). These therapeutic approaches include the use of site-specific ligands, receptors and cytokines, disruption of dominant fusion leukemogenic proteins, chromatin remodeling and combining the above with cytotoxic chemotherapy. With the exception of cytotoxic chemotherapy, the above therapeutic strategies do not significantly affect normal hematopoiesis and their combinations have been shown to be synergistic in inducing myeloid differentiation and apoptosis in several AML cell lines and in patients with APL. These approaches are, in general, non-cross resistant and should be well tolerated particularly in elderly patients with AML. Clinical studies which include biologic end points for differentiation induction, histone acetylation and selective apoptosis are presently in development to evaluate these strategies in the treatment of AML.