. 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

Petter S Woll¹, Una Kjällquist², Onima Chowdhury¹, Helen Doolittle¹, David C Wedge³, Supat Thongjuea¹, Rikard Erlandsson², Mtakai Ngara⁴, Kristina Anderson⁵, Qiaolin Deng⁴, Adam J Mead¹, Laura Stenson¹, Alice Giustacchini¹, Sara Duarte¹, Eleni Giannoulatou⁶, Stephen Taylor⁶, Mohsen Karimi⁷, Christian Scharenberg⁷, Teresa Mortera-Blanco⁷, Iain C Macaulay¹, Sally-Ann Clark¹, Ingunn Dybedal⁸, Dag Josefsen⁵, Pierre Fenaux⁹, Peter Hokland¹⁰, Mette S Holm¹⁰, Mario Cazzola¹¹, Luca Malcovati¹¹, Sudhir Tauro¹², David Bowen¹³, Jacqueline Boultwood¹⁴, Andrea Pellagatti¹⁴, John E Pimanda¹⁵, Ashwin Unnikrishnan¹⁵, Paresh Vyas¹⁶, Gudrun Göhring¹⁷, Brigitte Schlegelberger¹⁷, Magnus Tobiasson⁷, Gunnar Kvalheim⁵, Stefan N Constantinescu¹⁸, Claus Nerlov¹⁹, Lars Nilsson²⁰, Peter J Campbell³, Rickard Sandberg⁴, Elli Papaemmanuil³, Eva Hellström-Lindberg⁷, Sten Linnarsson², Sten Eirik W Jacobsen²¹

Affiliations

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

PMID: 24835589
DOI: 10.1016/j.ccr.2014.03.036

Free article

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

Petter S Woll et al. Cancer Cell. 2014.

Free article

. 2014 Jun 16;25(6):794-808.

doi: 10.1016/j.ccr.2014.03.036. Epub 2014 May 15.

Authors

Affiliations

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

PMID: 24835589
DOI: 10.1016/j.ccr.2014.03.036

Erratum in

Cancer Cell. 2014 Jun 16;25(6):861
Cancer Cell. 2015 Apr 13;27(4):603-5

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.

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Comment in

MDS is a stem cell disorder after all.
Jaiswal S, Ebert BL. Jaiswal S, et al. Cancer Cell. 2014 Jun 16;25(6):713-4. doi: 10.1016/j.ccr.2014.06.001. Cancer Cell. 2014. PMID: 24937455

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

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Comment in

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Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

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Miscellaneous