title: Dependence of acute myeloid leukemia on adhesion within the bone marrow microenvironment.
abstract: Acute myeloid leukemia (AML) cells home to the endosteal region of the bone marrow. They interact with bone marrow stromal components including extracellular matrix proteins, glycosaminoglycans, and stromal cells, by which they derive proliferative and growth inhibitory signals. Furthermore, adhesion to marrow stroma confers chemotherapy drug resistance and thereby promotes leukemia survival. A subpopulation of the leukemic blasts, known as leukemia stem cells, that are capable of propagating the leukemia, remain sheltered in the bone marrow microenvironment, exhibit resistance to chemotherapy, and serve as the origin of relapse after a variable period of remission. Detachment of these cells from the bone marrow in combination with chemotherapy may improve the outcome of therapy for AML.
authors.affiliation: Division of Hematology, Institute for Stem Cell and Regenerative Medicine, University of Washington, Campus Box 358056, 815 Mercer Street N415, Seattle, WA 98109, USA. pbecker@u.washington.edu
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Becker
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000737:chemistry* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D016326:Extracellular Matrix Proteins / Q000737:chemistry; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000737:chemistry; D019038:Platelet Glycoprotein GPIb-IX Complex; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000737:chemistry; D019707:Receptors, Chemokine / Q000737:chemistry; D015398:Signal Transduction; D017154:Stromal Cells / Q000737:chemistry; D059016:Tumor Microenvironment
chemical_list: C497483:CD44 protein, human; C527276:CXCR4 protein, human; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; C094990:adhesion receptor