title: Targeting the CXCL12/CXCR4 axis in acute myeloid leukemia: from bench to bedside.
abstract: The interactions between the cancerous cells of acute myeloid leukemia (AML) and the bone marrow (BM) microenvironment have been postulated to be important for resistance to chemotherapy and disease relapse in AML. The chemokine receptor CXC chemokine receptor 4 (CXCR4) and its ligand, CXC motif ligand 12 (CXCL12), also known as stromal cell-derived factor 1α, are key mediators of this interaction. CXCL12 is produced by the BM microenvironment, binds and activates its cognate receptor CXCR4 on leukemic cells, facilitates leukemia cell trafficking and homing in the BM microenvironment, and keeps leukemic cells in close contact with the stromal cells and extracellular matrix that constitutively generate growth-promoting and anti-apoptotic signals. Indeed, a high level of CXCR4 expression on AML blasts is known to be associated with poor prognosis. Recent preclinical and clinical studies have revealed the safety and potential clinical utility of targeting the CXCL12/CXCR4 axis in AML with different classes of drugs, including small molecules, peptides, and monoclonal antibodies. In this review, we describe recent evidence of targeting these leukemia-stroma interactions, focusing on the CXCL12/CXCR4 axis. Related early phase clinical studies will be also introduced.
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Byung-Sik
authors.initials: BS
authors.lastname: Cho
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hee-Je
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D057170:Translational Research, Biomedical; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4
keywords: CXCL12; CXCR4; Leukemia, myeloid, acute