title: Effectiveness of AMD3100 in treatment of leukemia and solid tumors: from original discovery to use in current clinical practice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: 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.|Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin, 300193 China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Winship Cancer Institute, Emory University, Atlanta, GA 30322 USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: You
authors.affiliation: School of Public Health, Division of Health Systems, Management, and Policy, The University of Memphis, Memphis, TN 38152 USA.
authors.forename: Soumitra S
authors.initials: SS
authors.lastname: Bhuyan
authors.affiliation: 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.
authors.forename: Lei
authors.identifier: 0000-0001-7530-7427
authors.initials: L
authors.lastname: Dong
keywords: AMD3100; Breast cancer; Leukemia; Plerixafor; Tumor