title: CD98-Mediated Adhesive Signaling Enables the Establishment and Propagation of Acute Myelogenous Leukemia.
abstract: Acute myelogenous leukemia (AML) is an aggressive disease associated with drug resistance and relapse. To improve therapeutic strategies, it is critical to better understand the mechanisms that underlie AML progression. Here we show that the integrin binding glycoprotein CD98 plays a central role in AML. CD98 promotes AML propagation and lethality by driving engagement of leukemia cells with their microenvironment and maintaining leukemic stem cells. Further, delivery of a humanized anti-CD98 antibody blocks growth of patient-derived AML, highlighting the importance of this pathway in human disease. These findings indicate that microenvironmental interactions are key regulators of AML and that disrupting these signals with targeted inhibitors such as CD98 antibodies may be a valuable therapeutic approach for adults and children with this disease.
authors.affiliation: Department of Pharmacology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA; Moores Cancer Center, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
authors.forename: Jeevisha
authors.initials: J
authors.lastname: Bajaj
authors.affiliation: Department of Pharmacology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA; Moores Cancer Center, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Konuma
authors.affiliation: Department of Pharmacology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA; Moores Cancer Center, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
authors.forename: Nikki K
authors.initials: NK
authors.lastname: Lytle
authors.affiliation: Department of Pharmacology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA; Moores Cancer Center, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
authors.forename: Hyog Young
authors.initials: HY
authors.lastname: Kwon
authors.affiliation: Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
authors.forename: Jailal N
authors.initials: JN
authors.lastname: Ablack
authors.affiliation: Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Cantor
authors.affiliation: Division of Cell Therapy, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: David
authors.initials: D
authors.lastname: Rizzieri
authors.affiliation: Department of Haematology, Singapore General Hospital, Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
authors.forename: Charles
authors.initials: C
authors.lastname: Chuah
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, WA 98109, USA.
authors.forename: Vivian G
authors.initials: VG
authors.lastname: Oehler
authors.affiliation: Moores Cancer Center, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Department of Pathology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Broome
authors.affiliation: Moores Cancer Center, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Department of Medicine, Blood and Marrow Transplantation Division, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Ball
authors.affiliation: Igenica Biotherapeutics Inc., Burlingame, CA 94010, USA.
authors.forename: Edward H
authors.initials: EH
authors.lastname: van der Horst
authors.affiliation: Moores Cancer Center, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA. Electronic address: mhginsberg@ucsd.edu.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ginsberg
authors.affiliation: Department of Pharmacology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA; Moores Cancer Center, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA. Electronic address: treya@ucsd.edu.
authors.forename: Tannishtha
authors.initials: T
authors.lastname: Reya
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000494:pharmacology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D027261:Fusion Regulatory Protein-1 / Q000037:antagonists & inhibitors / Q000235:genetics*; D055786:Gene Knockout Techniques; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*
chemical_list: D000906:Antibodies; D027261:Fusion Regulatory Protein-1
keywords: CD98; SLC3A2; acute myelogenous leukemia; adhesion; cancer; cancer stem cell; imaging; integrin; leukemia; microenvironment