Effectiveness of AMD3100 in treatment of leukemia and solid tumors: from original discovery to use in current clinical practice.

Tao Liu,Shuo You,Lei Dong,Soumitra S Bhuyan,Xiaobo Li

doi:10.1186/s40164-016-0050-5

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.

Highlights

In 1981, the US Centers for Disease Control and Prevention (CDC) published the first official report on the acquired immune deficiency syndrome (AIDS) epidemic
It is used for a variety of disorders that depend on the interplay of C-X-C chemokine receptor type 4 (CXCR4) with its agonist CXCL12 including leukemia and breast cancer
Current evidence indicates adhesion or mobilization of hematopoietic stem and progenitor cell (HSPC) is dependent on CXCL12 concentrations in the blood and the bone marrow that act via CXCR4 signaling [26]

Summary

Introduction

In 1981, the US Centers for Disease Control and Prevention (CDC) published the first official report on the acquired immune deficiency syndrome (AIDS) epidemic. AMD3100 is not limited to mobilization of HSCs. It is used for a variety of disorders that depend on the interplay of CXCR4 with its agonist CXCL12 ( called: SDF-1) including leukemia and breast cancer. Clinical data show less toxicity compared with HIV infections given the short time frame of administration of AMD3100 to initiate mobilization of hematopoietic stem and progenitors (HSPCs).

Results

Conclusion