Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo.
- 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.
- Macaulay I. C.
- Clark S. A.
- Dybedal I.
- Josefsen D.
- Fenaux P.
- Hokland P.
- Holm M. S.
- Tauro S.
- Bowen D.
- Boultwood J.
- Pellagatti A.
- Pimanda J. E.
- Unnikrishnan A.
- Vyas P.
- Göhring G.
- Schlegelberger B.
- Tobiasson M.
- Kvalheim G.
- Constantinescu S. N.
- Nerlov C.
- Nilsson L.
- Campbell P. J.
- Sandberg R. 4
- Papaemmanuil E.
- Hellström Lindberg E.
- Linnarsson S.
- Jacobsen S. E.
- CAZZOLA, MARIO
- MALCOVATI, LUCA
DOIAbstract
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 l...
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