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Cancer Cell. 2014 Jun 16;25(6):794-808. doi: 10.1016/j.ccr.2014.03.036. Epub 2014 May 15.

Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo.

Author information

  • 1Haematopoietic Stem Cell Biology Laboratory, MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
  • 2Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 65 Stockholm, Sweden.
  • 3Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA Cambridge, UK.
  • 4Ludwig Institute for Cancer Research and Department of Cell and Molecular Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
  • 5Department of Cellular Therapy, Norwegian Radium Hospital, Oslo University Hospital, 0130 Oslo, Norway.
  • 6Computational Biology Research Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
  • 7Center for Hematology and Regenerative Medicine, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
  • 8Department of Hematology, Oslo University Hospital, Rikshospitalet, 0130 Oslo, Norway.
  • 9Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'hématologie clinique, 93000 Bobigny, France.
  • 10Department of Hematology, Aarhus University Hospital, 8000 Aarhus, Denmark.
  • 11Department of Molecular Medicine, University of Pavia, and Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
  • 12Division of Medical Sciences, University of Dundee, Dundee DD1 9SY, Scotland, UK.
  • 13St. James Institute of Oncology, St. James Hospital, Leeds LS9 7TF, UK.
  • 14Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DU, UK.
  • 15Lowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney 2052, Australia.
  • 16MRC Molecular Haematology Unit, Department of Haematology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Oxford University Hospital, NHS Trust, Oxford OX3 9DU, UK.
  • 17Institute of Cell and Molecular Pathology, Hannover Medical School, 30625 Hannover, Germany.
  • 18Ludwig Institute for Cancer Research and de Duve Institute, Université Catholique de Louvain, 1200 Brussels, Belgium.
  • 19MRC Molecular Haematology Unit, Department of Haematology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
  • 20Skåne University Hospital, Lund 221 00, Sweden.
  • 21Haematopoietic Stem Cell Biology Laboratory, MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Departments of Cell and Molecular Biology, Medicine Huddinge, and Laboratory Medicine, Huddinge, Karolinska Institutet and Center for Hematology and Regenerative Medicine, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. Electronic address: sten.jacobsen@imm.ox.ac.uk.

Erratum in

  • Cancer Cell. 2014 Jun 16;25(6):861.

Abstract

Evidence for distinct human cancer stem cells (CSCs) remains contentious and the degree to which different cancer cells contribute to propagating malignancies in patients remains unexplored. In low- to intermediate-risk myelodysplastic syndromes (MDS), we establish the existence of rare multipotent MDS stem cells (MDS-SCs), and their hierarchical relationship to lineage-restricted MDS progenitors. All identified somatically acquired genetic lesions were backtracked to distinct MDS-SCs, establishing their distinct MDS-propagating function in vivo. In isolated del(5q)-MDS, acquisition of del(5q) preceded diverse recurrent driver mutations. Sequential analysis in del(5q)-MDS revealed genetic evolution in MDS-SCs and MDS-progenitors prior to leukemic transformation. These findings provide definitive evidence for rare human MDS-SCs in vivo, with extensive implications for the targeting of the cells required and sufficient for MDS-propagation.

Copyright © 2014 Elsevier Inc. All rights reserved.

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PMID:
24835589
[PubMed - indexed for MEDLINE]
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