Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias

Chaudhury, S. et al. (2018) Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias. Nature Communications, 9, 5280. (doi:10.1038/s41467-018-07584-1) (PMID:30538250) (PMCID:PMC6290074)

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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 cell interaction gene signature, highlighting two genes, RGS10 and FAM26F as prognostically significant. This work advances our understanding of paediatric AML biology, and provides murine models that offer the potential for developing paediatric specific therapeutic strategies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Silvestre, Ms Joana and Gibson, Professor Brenda and Prendergast, Dr Aine and Keeshan, Dr Karen and Chaudhury, Dr Shahzya and O'Connor, Ms Caitriona and Sarrou, Evgenia and Canete Sanchez, Mrs Ana Elodia and Johnston, Dr Pamela
Authors: Chaudhury, S., O'Connor, C., Cañete, A., Bittencourt-Silvestre, J., Sarrou, E., Prendergast, Á., Choi, J., Johnston, P., Wells, C. A., Gibson, B., and Keeshan, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Nature Communications 9: 5280
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
696321Development Award: Measurement of Small Molecule Pharmacokinetics in invasive Regions of GlioblastomaAnthony ChalmersCancer Research UK (CRUK)C596/A18076ICS - CLINICAL TRIALS RESEARCH

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