title: Adipocytes cause leukemia cell resistance to daunorubicin via oxidative stress response.
abstract: Adipocytes promote cancer progression and impair treatment, and have been shown to protect acute lymphoblastic leukemia (ALL) cells from chemotherapies. Here we investigate whether this protection is mediated by changes in oxidative stress. Co-culture experiments showed that adipocytes protect ALL cells from oxidative stress induced by drugs or irradiation. We demonstrated that ALL cells induce intracellular ROS and an oxidative stress response in adipocytes. This adipocyte oxidative stress response leads to the secretion of soluble factors which protect ALL cells from daunorubicin (DNR). Collectively, our investigation shows that ALL cells elicit an oxidative stress response in adipocytes, leading to adipocyte protection of ALL cells against DNR.
authors.affiliation: Diabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Diabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Tucci
authors.affiliation: Diabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: Jean-Hugues
authors.initials: JH
authors.lastname: Parmentier
authors.affiliation: Department of Biostatistics, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Ji
authors.affiliation: Diabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Behan
authors.affiliation: Division of Hematology/Oncology and Bone Marrow Transplant, Children's Hospital Los Angeles, Los Angeles, CA, USA.|Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Heisterkamp
authors.affiliation: Diabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, USA.|Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Mittelman
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D017382:Reactive Oxygen Species; D005978:Glutathione; D003630:Daunorubicin
keywords: ALL; adipocyte; drug resistance; glutathione; oxidative stress