Long-term in vitro maintenance of clonal abundance and leukaemia-initiating potential in acute lymphoblastic leukaemia

D Pal, H J Blair, A Elder, K Dormon, K J Rennie, D J L Coleman, J Weiland, K S Rankin, A Filby, O Heidenreich, J Vormoor

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)
6 Downloads (Pure)

Abstract

Lack of suitable in vitro culture conditions for primary acute lymphoblastic leukaemia (ALL) cells severely impairs their experimental accessibility and the testing of new drugs on cell material reflecting clonal heterogeneity in patients. We show that Nestin-positive human mesenchymal stem cells (MSCs) support expansion of a range of biologically and clinically distinct patient-derived ALL samples. Adherent ALL cells showed an increased accumulation in the S phase of the cell cycle and diminished apoptosis when compared with cells in the suspension fraction. Moreover, surface expression of adhesion molecules CD34, CDH2 and CD10 increased several fold. Approximately 20% of the ALL cells were in G0 phase of the cell cycle, suggesting that MSCs may support quiescent ALL cells. Cellular barcoding demonstrated long-term preservation of clonal abundance. Expansion of ALL cells for >3 months compromised neither feeder dependence nor cancer initiating ability as judged by their engraftment potential in immunocompromised mice. Finally, we demonstrate the suitability of this co-culture approach for the investigation of drug combinations with luciferase-expressing primograft ALL cells. Taken together, we have developed a preclinical platform with patient-derived material that will facilitate the development of clinically effective combination therapies for ALL.

Original languageEnglish
Pages (from-to)1691-1700
Number of pages10
JournalLeukemia
Volume30
Issue number8
Early online date10 Jun 2016
DOIs
Publication statusPublished - Aug 2016
Externally publishedYes

Fingerprint

Dive into the research topics of 'Long-term in vitro maintenance of clonal abundance and leukaemia-initiating potential in acute lymphoblastic leukaemia'. Together they form a unique fingerprint.

Cite this