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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Chaudhury S,O'Connor C,Cañete A,Bittencourt-Silvestre J,Sarrou E,Prendergast Á,Choi J,Johnston P,Wells CA,Gibson B,Keeshan K

doi

10.1038/s41467-018-07584-1

subject

Has Abstract

pub_date

2018-12-11 00:00:00

pages

5280

issue

1

issn

2041-1723

pii

10.1038/s41467-018-07584-1

journal_volume

9

pub_type

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