title: The role of microenvironment and immunity in drug response in leukemia.
abstract: Leukemia is a cancer of the white blood cells, with over 54,000 new cases per year diagnosed worldwide and a 5-year survival rate below 60%. This highlights a need for research into the mechanisms behind its etiology and causes of therapy failure. The bone marrow microenvironment, in which adult stem cells are maintained in healthy individuals, has been implicated as a source of chemoresistance and disease relapse. Here the various ways that the microenvironment can contribute to the resistance and persistence of leukemia are discussed. The targeting of the microenvironment by leukemia cells to create an environment more suitable for cancer progression is described. The role of soluble factors, drug transporters, microvesicles, as well as the importance of direct cell-cell contact, in addition to the effects of inflammation and immune surveillance in microenvironment-mediated drug resistance are discussed. An overview of the clinical potential of translating research findings to patients is also provided. Understanding of and further research into the role of the bone marrow microenvironment in leukemia progression and relapse are crucial towards developing more effective treatments and reduction in patient morbidity. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.
authors.affiliation: School of Environment and Life Sciences, University of Salford, United Kingdom.
authors.forename: Emyr
authors.initials: E
authors.lastname: Bakker
authors.affiliation: King Saud University, Saudi Arabia.
authors.forename: Malak
authors.initials: M
authors.lastname: Qattan
authors.affiliation: School of Environment and Life Sciences, University of Salford, United Kingdom.
authors.forename: Luciano
authors.initials: L
authors.lastname: Mutti
authors.affiliation: School of Pharmacy, University of Manchester, United Kingdom.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Demonacos
authors.affiliation: School of Environment and Life Sciences, University of Salford, United Kingdom. Electronic address: M.Krstic-Demonacos@salford.ac.uk.
authors.forename: Marija
authors.initials: M
authors.lastname: Krstic-Demonacos
mesh_terms: D000970:Antineoplastic Agents / Q000145:classification / Q000276:immunology / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007938:Leukemia / Q000188:drug therapy* / Q000276:immunology; D018448:Models, Immunological; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer; Immune surveillance; Inflammation; Leukemia; Microenvironment; Novel therapeutics