Laboratory of Cellular and Molecular Hemato-Oncology, Program of Molecular Hemato-Oncology, Brazilian National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil.
Laboratory of Cellular and Molecular Hemato-Oncology, Program of Molecular Hemato-Oncology, Brazilian National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil.
Blood Rev. 2020 Sep;43:100671. doi: 10.1016/j.blre.2020.100671. Epub 2020 Feb 24.
Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the BCR-ABL oncoprotein, known to drive leukemogenesis by orchestrating multiple signaling pathways ultimately involved in cell survival. Despite successful response rates of CML patients to tyrosine kinase inhibitors (TKIs), resistance eventually arises due to BCR-ABL-dependent and independent mechanisms. Survivin is an inhibitor of apoptosis protein acting in the interface between apoptosis deregulation and cell cycle progression. In CML, high levels of survivin have been associated with late stages of disease and therapy resistance. In this review, we provide an overview of important aspects concerning survivin subcellular localization and expression pattern in CML patients and cell lines. Moreover, we highlight the relevance of molecular networks involving survivin for disease progression and treatment resistance. Finally, we discuss the mechanisms accounting for survivin overexpression, as well as novel therapeutic interventions that have been designed to counteract survivin-associated malignancy in CML.
慢性髓细胞白血病（CML）是一种骨髓增生性疾病，其特征是存在 BCR-ABL 癌蛋白，该癌蛋白通过协调最终参与细胞存活的多个信号通路来驱动白血病的发生。尽管 CML 患者对酪氨酸激酶抑制剂（TKI）的反应率很高，但由于 BCR-ABL 依赖性和非依赖性机制，最终会产生耐药性。Survivin 是一种凋亡抑制蛋白，作用于凋亡失调和细胞周期进展之间的界面。在 CML 中，高水平的 survivin 与疾病的晚期和治疗耐药性有关。在这篇综述中，我们提供了有关 survivin 亚细胞定位和表达模式在 CML 患者和细胞系中的重要方面的概述。此外，我们强调了涉及 survivin 的分子网络对于疾病进展和治疗耐药性的相关性。最后，我们讨论了导致 survivin 过表达的机制，以及为了对抗 CML 中与 survivin 相关的恶性肿瘤而设计的新型治疗干预措施。
