Abundant and equipotent founder cells establish and maintain acute lymphoblastic leukaemia

Research output: Contribution to journalArticle

DOI

Authors

  • A Elder
  • S Bomken
  • I Wilson
  • H J Blair
  • S Cockell
  • F Ponthan
  • K Dormon
  • D Pal
  • O Heidenreich
  • J Vormoor

External departments

  • Newcastle University
  • Newcastle upon Tyne Hospitals NHS Foundation Trust

Details

Original languageEnglish
Pages (from-to)2577-2586
Number of pages10
JournalLeukemia
Volume31
Issue number12
Early online date10 May 2017
DOIs
Publication statusPublished - Dec 2017
Externally publishedYes
Publication type

Research output: Contribution to journalArticle

Abstract

High frequencies of blasts in primary acute lymphoblastic leukaemia (ALL) samples have the potential to induce leukaemia and to engraft mice. However, it is unclear how individual ALL cells each contribute to drive leukaemic development in a bulk transplant and the extent to which these blasts vary functionally. We used cellular barcoding as a fate mapping tool to track primograft ALL blasts in vivo. Our results show that high numbers of ALL founder cells contribute at similar frequencies to leukaemic propagation over serial transplants, without any clear evidence of clonal succession. These founder cells also exhibit equal capacity to home and engraft to different organs, although stochastic processes may alter the composition in restrictive niches. Our findings enhance the stochastic stem cell model of ALL by demonstrating equal functional abilities of singular ALL blasts and show that successful treatment strategies must eradicate the entire leukaemic cell population.

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