Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon.
Stem Cells Int. 2013;2013:724360. doi: 10.1155/2013/724360. Epub 2013 Jul 9.
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder. Current targeted therapies designed to inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein have made a significant breakthrough in the treatment of CML patients. However, CML remains a chronic disease that a patient must manage for life. Although tyrosine kinase inhibitors (TKI) therapy has completely transformed the prognosis of CML, it has made the therapeutic management more complex. The interruption of TKI treatment results in early disease progression because it does not eliminate quiescent CML stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML to achieve a permanent cure, and to allow TKI interruption. This review summarizes recent research done on alternative targeted therapies with a particular focus on some important signaling pathways (such as Alox5, Hedgehog, Wnt/b-catenin, autophagy, and PML) that have the potential to target CML stem cells and potentially provide cure for CML.
慢性髓性白血病（CML）是一种克隆性骨髓增生性疾病。目前旨在抑制 BCR-ABL 癌蛋白酪氨酸激酶活性的靶向治疗在 CML 患者的治疗中取得了重大突破。然而，CML 仍然是一种需要患者终生管理的慢性疾病。尽管酪氨酸激酶抑制剂（TKI）治疗彻底改变了 CML 的预后，但它使治疗管理更加复杂。TKI 治疗的中断会导致早期疾病进展，因为它不能消除静止的 CML 干细胞，这些干细胞仍然是疾病复发的潜在来源。这凸显了需要开发新的 CML 治疗策略以实现永久治愈并允许 TKI 中断的必要性。本综述总结了最近在替代靶向治疗方面的研究进展，特别关注一些重要的信号通路（如 Alox5、Hedgehog、Wnt/b-catenin、自噬和 PML），这些信号通路有可能靶向 CML 干细胞，并有可能为 CML 提供治愈方法。
