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

Petter S. Woll, Una Kjällquist, Onima Chowdhury, Helen Doolittle, David C. Wedge, Supat Thongjuea, Rikard Erlandsson, Mtakai Ngara, Kristina Anderson, Qiaolin Deng, Adam J. Mead, Laura Stenson, Alice Giustacchini, Sara Duarte, Eleni Giannoulatou, Stephen Taylor, Mohsen Karimi, Christian Scharenberg, Teresa Mortera-Blanco, Iain C. MacaulaySally-Ann Clark, Ingunn Dybedal, Dag Josefsen, Pierre Fenaux, Peter Hokland, Mette S. Holm, Mario Cazzola, Luca Malcovati, Sudhir Tauro, David Bowen, Jacqueline Boultwood, Andrea Pellagatti, John E. Pimanda, Ashwin Unnikrishnan, Paresh Vyas, Gudrun Göhring, Brigitte Schlegelberger, Magnus Tobiasson, Gunnar Kvalheim, Stefan N. Constantinescu, Claus Nerlov, Lars Nilsson, Peter J. Campbell, Rikard Sandberg, Elli Papaemmanuil, Eva Hellström-Lindberg, Sten Linnarsson, Sten Erik W. Jacobsen

    Research output: Contribution to journalArticle

    171 Citations (Scopus)

    Abstract

    Evidence for distinct human cancer stem cells (CSCs) remains contentious and the degree to which differentcancer 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 invivo. 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 invivo, with extensive implications for the targeting of the cells required and sufficient for MDS-propagation.
    Original languageEnglish
    Pages (from-to)794-808
    Number of pages15
    JournalCancer Cell
    Volume25
    Issue number6
    DOIs
    Publication statusPublished - 16 Jun 2014

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  • Cite this

    Woll, P. S., Kjällquist, U., Chowdhury, O., Doolittle, H., Wedge, D. C., Thongjuea, S., Erlandsson, R., Ngara, M., Anderson, K., Deng, Q., Mead, A. J., Stenson, L., Giustacchini, A., Duarte, S., Giannoulatou, E., Taylor, S., Karimi, M., Scharenberg, C., Mortera-Blanco, T., ... Jacobsen, S. E. W. (2014). Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo. Cancer Cell, 25(6), 794-808. https://doi.org/10.1016/j.ccr.2014.03.036