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( \! X+ b9 W2 J7 c1 l7 d- Y0 ddoi:10.1016/j.ccr.2014.03.036. I' a' g" _" F) V a x
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* h5 A. N" y2 xMyelodysplastic Syndromes Are Propagated by Rare and Distinct Human Cancer Stem Cells In Vivo
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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.
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# Z8 {* n$ B: WEvidence 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.* a5 x: \- _' L4 S1 a f# }5 w
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发表于 2014-5-21 20:44
发表于 2014-5-21 23:17
