| Literature DB >> 24835589 |
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.
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.Entities:
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Year: 2014 PMID： 24835589 DOI： 10.1016/j.ccr.2014.03.036
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743