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Activation of GPR44 decreases severity of myeloid leukemia via specific targeting of leukemia initiating stem cells.
Qian, Fenghua; Nettleford, Shaneice K; Zhou, Jiayan; Arner, Brooke E; Hall, Molly A; Sharma, Arati; Annageldiyev, Charyguly; Rossi, Randy M; Tukaramrao, Diwakar B; Sarkar, Deborpita; Hegde, Shailaja; Gandhi, Ujjawal H; Finch, Emily R; Goodfield, Laura; Quickel, Michael D; Claxton, David F; Paulson, Robert F; Prabhu, K Sandeep.
Afiliación
  • Qian F; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
  • Nettleford SK; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
  • Zhou J; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
  • Arner BE; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
  • Hall MA; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
  • Sharma A; Department of Medicine, Division of Hematology and Oncology, Penn State Cancer Institute, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
  • Annageldiyev C; Department of Medicine, Division of Hematology and Oncology, Penn State Cancer Institute, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
  • Rossi RM; Transgenic Core Facility, Huck Institute of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
  • Tukaramrao DB; Department of Medicine, Division of Hematology and Oncology, Penn State Cancer Institute, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
  • Sarkar D; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
  • Hegde S; Hoxworth Blood Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
  • Gandhi UH; Department of Hematology and Oncology, University of North Carolina Health, Cary, NC 27518, USA.
  • Finch ER; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Goodfield L; Immunooncology Division, Bicycle Therapeutics, Boston, MA 02140, USA.
  • Quickel MD; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
  • Claxton DF; Department of Medicine, Division of Hematology and Oncology, Penn State Cancer Institute, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
  • Paulson RF; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: rfp5@psu.edu.
  • Prabhu KS; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: ksp4@psu.edu.
Cell Rep ; 42(7): 112794, 2023 07 25.
Article en En | MEDLINE | ID: mdl-37459233
ABSTRACT
Relapse of acute myeloid leukemia (AML) remains a significant concern due to persistent leukemia-initiating stem cells (LICs) that are typically not targeted by most existing therapies. Using a murine AML model, human AML cell lines, and patient samples, we show that AML LICs are sensitive to endogenous and exogenous cyclopentenone prostaglandin-J (CyPG), Δ12-PGJ2, and 15d-PGJ2, which are increased upon dietary selenium supplementation via the cyclooxygenase-hematopoietic PGD synthase pathway. CyPGs are endogenous ligands for peroxisome proliferator-activated receptor gamma and GPR44 (CRTH2; PTGDR2). Deletion of GPR44 in a mouse model of AML exacerbated the disease suggesting that GPR44 activation mediates selenium-mediated apoptosis of LICs. Transcriptomic analysis of GPR44-/- LICs indicated that GPR44 activation by CyPGs suppressed KRAS-mediated MAPK and PI3K/AKT/mTOR signaling pathways, to enhance apoptosis. Our studies show the role of GPR44, providing mechanistic underpinnings of the chemopreventive and chemotherapeutic properties of selenium and CyPGs in AML.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Selenio / Leucemia Mieloide Aguda Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Selenio / Leucemia Mieloide Aguda Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos