title: CD99 is a therapeutic target on disease stem cells in myeloid malignancies.
abstract: Acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS) are initiated and sustained by self-renewing malignant stem cells; thus, eradication of AML and MDS stem cells is required for cure. We identified CD99 as a cell surface protein frequently overexpressed on AML and MDS stem cells. Expression of CD99 allows for prospective separation of leukemic stem cells (LSCs) from functionally normal hematopoietic stem cells in AML, and high CD99 expression on AML blasts enriches for functional LSCs as demonstrated by limiting dilution xenotransplant studies. Monoclonal antibodies (mAbs) targeting CD99 induce the death of AML and MDS cells in a SARC family kinase-dependent manner in the absence of immune effector cells or complement, and anti-CD99 mAbs exhibit antileukemic activity in AML xenografts. These data establish CD99 as a marker of AML and MDS stem cells, as well as a promising therapeutic target in these disorders.
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.|Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Chung
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Eng
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Wenhuo
authors.initials: W
authors.lastname: Hu
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.|Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA.
authors.forename: Mona
authors.initials: M
authors.lastname: Khalaj
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell School of Medicine, New York, NY 10065, USA.
authors.forename: Francine E
authors.initials: FE
authors.lastname: Garrett-Bakelman
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Montreh
authors.initials: M
authors.lastname: Tavakkoli
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.|Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Levine
authors.affiliation: Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Carroll
authors.affiliation: Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Klimek
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell School of Medicine, New York, NY 10065, USA.
authors.forename: Ari M
authors.initials: AM
authors.lastname: Melnick
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. christopher.park@nyumc.org.|Departments of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Park
mesh_terms: D000071443:12E7 Antigen / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D008297:Male; D051379:Mice; D009190:Myelodysplastic Syndromes / Q000378:metabolism*; D009368:Neoplasm Transplantation; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D000071443:12E7 Antigen; D000911:Antibodies, Monoclonal; C061828:CD99 protein, human