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doi:10.1016/j.ccr.2014.03.036/ N5 I6 d$ [8 G4 K6 k
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Myelodysplastic Syndromes Are Propagated by Rare and Distinct Human Cancer Stem Cells In Vivo* X% S. _) _1 r6 i* X
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Petter S. Woll, Una Kj?llquist, Onima Chowdhury, Helen Doolittle, David C. Wedge, Supat Thongjuea, Rikard Erlandsson, Mtakai Ngara, Kristina Anderson,.et al., i6 e. t; ~ u" v9 E6 J
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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.! g) y; _# p$ X* {; `; u
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