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LukS-PV,a component of Panton-Valentine leukocidin,exerts potent activity against acute myeloid leukemia in vitro and in vivo
Affiliation:1. Department of Laboratory Medicine, Anhui Provincial Hospital, Anhui Medical University, Hefei 230032, PR China;2. Clinical Laboratory Center, the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, PR China;3. Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Department of Microbiology and Parasitology, Anhui Medical University, Hefei 230032, PR China;4. School of Medicine, Shandong University, Jinan, PR China;1. Infection Control Program and WHO Collaborating Centre on Patient Safety, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland;2. Department of Infection Control, Dong Guan Hospital of Traditional Chinese Medicine, Dong Guan City, Guang Dong Province, China;3. Institute of Global Health, Faculty of Medicine, University of Geneva, Geneva, Switzerland;4. Department Infection Control, Dong Guan Tung Wah Hospital, Dong Guan City, Guang Dong Province, China;5. Dongguan Nosocomial Infection Control and Quality Improvement Centre, Dong Guan City, Guang Dong Province, China;6. Imperial College London, London, UK;1. Federal Institute for Drugs and Medical Devices, L2-Biosafety-Laboratory;2. Federal Institute for Drugs and Medical Devices, Biostatistics Unit, Bonn;3. Robert Koch Institute, Wernigerode, Germany;1. Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA;2. Keenan Research Centre, St Michael’s Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada;3. Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada;4. Janssen Research & Development LLC, 1400 McKean Road, Spring House, PA 19477, USA;5. Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA;6. Department of Pathology, New York University School of Medicine, New York, NY, USA;7. Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA;8. Office of Collaborative Sciences, NYU School of Medicine, New York, NY, USA;9. Department of Pathology, NYU School of Medicine, New York, NY, USA;10. Department of Pediatrics, University of Pennsylvania, Philadelphia, PA, USA;11. Division of Neonatology, Children''s Hospital of Philadelphia, Philadelphia, PA, USA;12. Division of Infectious Diseases, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA
Abstract:LukS-PV, a component of Panton-Valentine leukocidin (PVL) secreted by Staphylococcus aureus, has been shown to inhibit proliferation and induce apoptosis in acute myeloid leukemia (AML) THP-1 cells. Here we investigated anti-leukemia activities of LukS-PV in HL-60 cells, using in vitro assays to assess the ability of LukS-PV to mediate cell viability, apoptosis and differentiation; and developing a Severe Combined Immunodeficiency (SCID) mouse model of disseminated AML with the HL-60 cells to examine in vivo anti-leukemia activity. LukS-PV inhibited viability and induced differentiation and apoptosis in the HL-60 AML cell line. In the SCID mice, LukS-PV potently inhibited tumor growth, decreased tumor cell infiltration into peripheral blood and tissues, and significantly increased mean survival time. No severe adverse effects, such as death, weight loss, or pathological changes in livers or spleens were observed in the toxicity test group. These results indicate that LukS-PV may be a novel and effective chemotherapeutic agent against AML.
Keywords:Acute myeloid leukemia  Panton-Valentine leukocidin  Apoptosis  Differentiation  Bacteriotoxin
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