title: The bone marrow microenvironment and leukemia: biology and therapeutic targeting.
abstract: Multiple studies have demonstrated that interaction with the bone marrow stromal microenvironment contributes to the survival of leukemia cells. One explanation for this phenomenon is the interaction between the cell surface receptors CXCR4 and CXCL12. Through CXCL12/CXCR4-mediated chemotaxis, leukemia cells migrate to microscopic niches within the bone marrow, which leads to increased proliferation and survival. Several studies have suggested that increased CXCR4 expression may portend a poor prognosis in various types of leukemia, possibly due to increased protection of leukemia cells by bone marrow stroma. A potential therapeutic strategy to overcome this stromal-mediated survival advantage is to target CXCR4. Inhibition of CXCR4 may allow leukemia cells to be released from bone marrow niches that confer resistance to chemotherapy and negate the survival benefit imparted by bone marrow stroma.
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Edward Allan R
authors.initials: EA
authors.lastname: Sison
authors.forename: Patrick
authors.initials: P
authors.lastname: Brown
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D001853:Bone Marrow / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000378:metabolism; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006410:Hematopoiesis; D006801:Humans; D007938:Leukemia / Q000628:therapy*; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D054377:Chemokine CXCL12; D010455:Peptides; D019718:Receptors, CXCR4