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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Petter S Woll
  • Una Kjällquist
  • Onima Chowdhury
  • Helen Doolittle
  • David C Wedge
  • Supat Thongjuea
  • Rikard Erlandsson
  • Mtakai Ngara
  • Kristina Anderson
  • Qiaolin Deng
  • Adam J Mead
  • Laura Stenson
  • Alice Giustacchini
  • Sara Duarte
  • Eleni Giannoulatou
  • Stephen Taylor
  • Mohsen Karimi
  • Christian Scharenberg
  • Teresa Mortera-Blanco
  • Iain C Macaulay
  • And 28 others
  • Sally-Ann Clark
  • Ingunn Dybedal
  • Dag Josefsen
  • Pierre Fenaux
  • Peter Hokland
  • Mette S Holm
  • Mario Cazzola
  • Luca Malcovati
  • Sudhir Tauro
  • David Bowen
  • Jacqueline Boultwood
  • Andrea Pellagatti
  • John E Pimanda
  • Ashwin Unnikrishnan
  • Paresh Vyas
  • Gudrun Göhring
  • Brigitte Schlegelberger
  • Magnus Tobiasson
  • Gunnar Kvalheim
  • Stefan N Constantinescu
  • Claus Nerlov
  • Lars Nilsson
  • Peter J Campbell
  • Rickard Sandberg
  • Elli Papaemmanuil
  • Eva Hellström-Lindberg
  • Sten Linnarsson
  • Sten Eirik W Jacobsen
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)794-808
JournalCancer Cell
Volume25
Issue number6
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes