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

Woll, Petter S; Kjällquist, Una; Chowdhury, Onima; Doolittle, Helen; Wedge, David C; Thongjuea, Supat; Erlandsson, Rikard; Ngara, Mtakai; Anderson, Kristina LU and Deng, Qiaolin, et al. (2014) In Cancer Cell 25(6). p.794-808
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... (More)
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. (Less)
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Cancer Cell
volume
25
issue
6
pages
794 - 808
publisher
Cell Press
external identifiers
  • pmid:24835589
  • wos:000337709600010
  • scopus:84902480315
ISSN
1878-3686
DOI
10.1016/j.ccr.2014.03.036
language
English
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yes
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bcdac88c-f35e-4d47-95cf-f461d2e759d7 (old id 4454340)
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http://www.ncbi.nlm.nih.gov/pubmed/24835589?dopt=Abstract
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2014-06-04 21:14:57
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2017-11-05 03:01:26
@article{bcdac88c-f35e-4d47-95cf-f461d2e759d7,
  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.},
  author       = {Woll, Petter S and Kjällquist, Una and Chowdhury, Onima and Doolittle, Helen and Wedge, David C and Thongjuea, Supat and Erlandsson, Rikard and Ngara, Mtakai and Anderson, Kristina and Deng, Qiaolin and Mead, Adam J and Stenson, Laura and Giustacchini, Alice and Duarte, Sara and Giannoulatou, Eleni and Taylor, Stephen and Karimi, Mohsen and Scharenberg, Christian and Mortera-Blanco, Teresa and Macaulay, Iain C and Clark, Sally-Ann and Dybedal, Ingunn and Josefsen, Dag and Fenaux, Pierre and Hokland, Peter and Holm, Mette S and Cazzola, Mario and Malcovati, Luca and Tauro, Sudhir and Bowen, David and Boultwood, Jacqueline and Pellagatti, Andrea and Pimanda, John E and Unnikrishnan, Ashwin and Vyas, Paresh and Göhring, Gudrun and Schlegelberger, Brigitte and Tobiasson, Magnus and Kvalheim, Gunnar and Constantinescu, Stefan N and Nerlov, Claus and Nilsson, Lars and Campbell, Peter J and Sandberg, Rickard and Papaemmanuil, Elli and Hellström-Lindberg, Eva and Linnarsson, Sten and Jacobsen, Sten Eirik W},
  issn         = {1878-3686},
  language     = {eng},
  number       = {6},
  pages        = {794--808},
  publisher    = {Cell Press},
  series       = {Cancer Cell},
  title        = {Myelodysplastic Syndromes Are Propagated by Rare and Distinct Human Cancer Stem Cells In Vivo.},
  url          = {http://dx.doi.org/10.1016/j.ccr.2014.03.036},
  volume       = {25},
  year         = {2014},
}