Liu Tao, Li Xiaobo, You Shuo, Bhuyan Soumitra S, Dong Lei
Division of Hematology/Oncology, Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, 1760 Haygood Drive NE, HSRB E363, Atlanta, GA 30322 USA.
Department of Oncology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Wuxi, 214400 Jiangsu People's Republic of China.
Exp Hematol Oncol. 2016 Jul 16;5:19. doi: 10.1186/s40164-016-0050-5. eCollection 2015.
AMD3100, also known as plerixafor, was originally developed as an anti-human immunodeficiency virus (HIV) drug, and later characterized as a C-X-C chemokine receptor type 4 (CXCR4) antagonist. Previous reviews have focused on the application of AMD3100 in the treatment of HIV, but a comprehensive evaluation of AMD3100 in the treatment of leukemia, solid tumor, and diagnosis is lacking. In this review, we broadly describe AMD3100, including the background, functional mechanism and clinical applications. Until the late 1990s, CXCR4 was known as a crucial factor for hematopoietic stem and progenitor cell (HSPC) retention in bone marrow. Subsequently, the action and synergy of plerixafor with Granulocyte-colony stimulating factor (G-CSF) led to the clinical approval of plerixafor as the first compound for mobilization of HSPCs. The amount of HSPC mobilization and the rapid kinetics promoted additional clinical uses. Recently, CXCR4/CXCL12 (C-X-C motif chemokine 12) axis was found to be involved in a variety of roles in tumors, including leukemic stem cell (LSC) homing and signaling transduction. Thus, CXCR4 targeting has been a treatment strategy against leukemia and solid tumors. Understanding this mechanism will help shed light on therapeutic potential for HIV infection, inflammatory diseases, stem-cell mobilization, leukemia, and solid tumors. Clarifying the CXCR4/CXCL12 axis and role of AMD3100 will help remove malignant cells from the bone marrow niche, rendering them more accessible to targeted therapeutic agents.
AMD3100，也被称为普乐沙福，最初是作为一种抗人类免疫缺陷病毒（HIV）药物开发的，后来被鉴定为一种CXC趋化因子受体4（CXCR4）拮抗剂。以往的综述主要聚焦于AMD3100在治疗HIV方面的应用，但缺乏对AMD3100在白血病、实体瘤治疗及诊断方面的全面评估。在本综述中，我们广泛描述了AMD3100，包括其背景、作用机制及临床应用。直到20世纪90年代末，CXCR4被认为是造血干细胞和祖细胞（HSPC）保留在骨髓中的关键因素。随后，普乐沙福与粒细胞集落刺激因子（G-CSF）的作用及协同作用导致普乐沙福作为首个用于动员HSPC的化合物获得临床批准。HSPC动员的数量及快速动力学促进了其更多的临床应用。最近，发现CXCR4/CXCL12（CXC基序趋化因子12）轴在肿瘤中发挥多种作用，包括白血病干细胞（LSC）归巢和信号转导。因此，靶向CXCR4一直是治疗白血病和实体瘤的一种策略。了解这一机制将有助于揭示其在HIV感染、炎症性疾病、干细胞动员、白血病和实体瘤治疗方面的潜力。阐明CXCR4/CXCL12轴及AMD3100的作用将有助于从骨髓微环境中清除恶性细胞，使其更容易被靶向治疗药物作用。
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