Journal article
Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias
S Chaudhury, C O’Connor, A Cañete, J Bittencourt-Silvestre, E Sarrou, Á Prendergast, J Choi, P Johnston, CA Wells, B Gibson, K Keeshan
Nature Communications | NATURE PUBLISHING GROUP | Published : 2018
Abstract
Acute myeloid leukaemia (AML) affects children and adults of all ages. AML remains one of the major causes of death in children with cancer and for children with AML relapse is the most common cause of death. Here, by modelling AML in vivo we demonstrate that AML is discriminated by the age of the cell of origin. Young cells give rise to myeloid, lymphoid or mixed phenotype acute leukaemia, whereas adult cells give rise exclusively to AML, with a shorter latency. Unlike adult, young AML cells do not remodel the bone marrow stroma. Transcriptional analysis distinguishes young AML by the upregulation of immune pathways. Analysis of human paediatric AML samples recapitulates a paediatric immune..
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Awarded by CHILDREN with CANCER UK
Funding Acknowledgements
We acknowledge the technical assistance of Jennifer Cassels and the flow cytometry core funding from the Kay Kendell Leukaemia Fund and The Howat Foundation. We thank Karen Dunn for technical assistance with animal experiments and the Cancer Research UK Glasgow Centre (C596/A18076) and the BSU facilities at the Cancer Research UK Beatson Institute (C596/A17196). We thank Francesco Marchesi, Lynn Stevenson, Lynn Oxford and Frazer Bell (Veterinary Diagnostic Services, School of Veterinary Medicine, University of Glasgow) for their technical assistance with histology and immunohistochemistry. We thank Tyrone Chen for processing all relevant datasets. We thank all staff at the Paul O'Gorman Leukaemia Research Centre for helpful suggestions and advice. We thank support from Children with Cancer UK (to K.K.), the Howat foundation (to K.K., C.O'C., A.C.), Yorkhill Children Cancer, Yorkhill Children's Leukaemia Research Fund (to E.S., S.C., A.P.) and the Friends of Paul O' Gorman (to J.B.S.).