Details

Autor(en) / Beteiligte

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

Titel

Myelodysplastic Syndromes Are Propagated by Rare and Distinct Human Cancer Stem Cells In Vivo

Ist Teil von

• Cancer cell, 2014-06, Vol.25 (6), p.794-808

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •MDS stem cells and progenitors are distinct and hierarchically related•Mutations in low-risk MDS originate exclusively in distinct and rare MDS stem cells•Mutations preceding AML transformation might confer self-renewal to MDS progenitors•del(5q) precedes acquisition of recurrent driver mutations in isolated del(5q) MDS Using functional analyses and backtracking of somatic genetic alterations, Woll et al. show that in low-intermediate risk human myelodysplastic syndromes (MDS) only the rare Lin−CD34+CD38−CD90+CD45RA− cells function as MDS-propagating cells.