Abundant and equipotent founder cells establish and maintain acute lymphoblastic leukaemia

Elder, A, Bomken, S, Wilson, I, Blair, H J, Cockell, S, Ponthan, F, Dormon, K, Pal, Deepali, Heidenreich, O and Vormoor, J (2017) Abundant and equipotent founder cells establish and maintain acute lymphoblastic leukaemia. Leukemia, 31 (12). pp. 2577-2586. ISSN 0887-6924

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Official URL: https://doi.org/10.1038/leu.2017.140

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.

Item Type: Article
Uncontrolled Keywords: Animals, Biomarkers, Tumor, Cell Transformation, Neoplastic/genetics, Clonal Evolution/genetics, Computational Biology/methods, Disease Models, Animal, Gene Expression Profiling, Heterografts, High-Throughput Nucleotide Sequencing, Humans, Mice, Models, Biological, Neoplastic Stem Cells/metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology
Subjects: A100 Pre-clinical Medicine
A300 Clinical Medicine
B100 Anatomy, Physiology and Pathology
B800 Medical Technology
B900 Others in Subjects allied to Medicine
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Rachel Branson
Date Deposited: 10 Mar 2020 09:56
Last Modified: 10 Mar 2020 10:00
URI: http://nrl.northumbria.ac.uk/id/eprint/42434

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