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miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
Lechman, Eric R; Gentner, Bernhard; Ng, Stanley W K; Schoof, Erwin M; van Galen, Peter; Kennedy, James A; Nucera, Silvia; Ciceri, Fabio; Kaufmann, Kerstin B; Takayama, Naoya; Dobson, Stephanie M; Trotman-Grant, Aaron; Krivdova, Gabriela; Elzinga, Janneke; Mitchell, Amanda; Nilsson, Björn; Hermans, Karin G; Eppert, Kolja; Marke, Rene; Isserlin, Ruth; Voisin, Veronique; Bader, Gary D; Zandstra, Peter W; Golub, Todd R; Ebert, Benjamin L; Lu, Jun; Minden, Mark; Wang, Jean C Y; Naldini, Luigi; Dick, John E.
Afiliação
  • Lechman ER; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Gentner B; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Hospital, Milan 20132, Italy; Vita Salute San Raffaele University, San Raffaele Scientific Institute, San Raffaele Hospital, Milan 20132, Italy; Hematology and Bone Marrow Transplantation Unit, San Raffaele Hospital, Milan 20132, Italy.
  • Ng SW; Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5G 2M9, Canada; The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
  • Schoof EM; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • van Galen P; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Kennedy JA; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2M9, Canada.
  • Nucera S; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Hospital, Milan 20132, Italy; Vita Salute San Raffaele University, San Raffaele Scientific Institute, San Raffaele Hospital, Milan 20132, Italy.
  • Ciceri F; Vita Salute San Raffaele University, San Raffaele Scientific Institute, San Raffaele Hospital, Milan 20132, Italy; Hematology and Bone Marrow Transplantation Unit, San Raffaele Hospital, Milan 20132, Italy.
  • Kaufmann KB; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Takayama N; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Dobson SM; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Trotman-Grant A; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Krivdova G; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Elzinga J; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Mitchell A; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Nilsson B; Department of Hematology and Transfusion Medicine, Lund University Hospital, Lund 221 84, Sweden.
  • Hermans KG; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Eppert K; Department of Pediatrics, McGill University and The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
  • Marke R; Laboratory of Pediatric Oncology, Radboud University Medical Center, Nijmegen, 6500 HB, Netherlands.
  • Isserlin R; The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
  • Voisin V; The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
  • Bader GD; The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
  • Zandstra PW; Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5G 2M9, Canada; The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
  • Golub TR; Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
  • Ebert BL; Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Lu J; Yale Stem Cell Center, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Minden M; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2M9, Canada.
  • Wang JC; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2M9, Canada.
  • Naldini L; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Hospital, Milan 20132, Italy; Vita Salute San Raffaele University, San Raffaele Scientific Institute, San Raffaele Hospital, Milan 20132, Italy.
  • Dick JE; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Research Tower, Room 8-301, 101 College Street, Toronto M5G 1L7, Canada. Elec
Cancer Cell ; 29(2): 214-28, 2016 Feb 08.
Article em En | MEDLINE | ID: mdl-26832662
ABSTRACT
To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Leucemia Mieloide Aguda / MicroRNAs Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Canadá
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Leucemia Mieloide Aguda / MicroRNAs Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Canadá