Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China.
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China;, Email:
Pharmazie. 2021 Dec 5;76(12):574-578. doi: 10.1691/ph.2021.1744.
Development of tyrosine kinase inhibitors (TKIs) achieved great success in the treatment of chronic phase chronic myeloid leukemia (CML). However, patients with CML still relapse without taking TKIs and cases in the accelerated phase or aggressive blast crisis rarely achieved deep response to TKIs. Drug resistance and persistence of leukemia stem cell (LSC) remain great challenges. BCR-ABL kinase dependent or independent mechanism of action are still far from being understood. To achieve a stable deep molecular response and treatment-free remission, finding new targets, eliminating LSC, reducing recurrence and improving prognosis are problems urgently to be solved. It is revealed that tumor microenvironment is crucial for survival, invasion and metastasis of tumor cells. As an adhesion molecule, CD44, a single-chain transmembrane glycoprotein, is not only being identified as a marker for cancer stem cells, but also plays a crucial role in microenvironmental communication and transmitting intracellular signaling for cell proliferation, differentiation, migration, and contributes to tumorigenesis. In this review, we focus on current data relevant to CD44, and outline CD44 structure, the regulation of CD44, functional properties of CD44 in survival, resistance, CML stem cells as well as the potential CD44-targeting therapy for CML management.
酪氨酸激酶抑制剂（TKIs）的发展在慢性期慢性髓性白血病（CML）的治疗中取得了巨大成功。然而，未服用 TKI 的 CML 患者仍会复发，加速期或侵袭性爆发性危象的病例很少对 TKI 产生深度反应。耐药性和白血病干细胞（LSC）的持续存在仍然是巨大的挑战。BCR-ABL 激酶依赖性或非依赖性作用机制仍远未被理解。为了实现稳定的深度分子反应和无治疗缓解，寻找新的靶点，消除 LSC，减少复发并改善预后是亟待解决的问题。已经揭示肿瘤微环境对于肿瘤细胞的存活、侵袭和转移至关重要。作为黏附分子，CD44 是一种单链跨膜糖蛋白，不仅被鉴定为癌症干细胞的标志物，而且在微环境通讯和传递细胞内信号以促进细胞增殖、分化、迁移方面发挥着关键作用，有助于肿瘤发生。在这篇综述中，我们重点介绍了与 CD44 相关的最新数据，并概述了 CD44 的结构、CD44 的调节、CD44 在存活、耐药性、CML 干细胞中的功能特性以及针对 CML 管理的潜在 CD44 靶向治疗。
