Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias.
Shahzya ChaudhuryCaitríona O'ConnorAna CañeteJoana Bittencourt-SilvestreEvgenia SarrouÁine PrendergastJarny ChoiPamela JohnstonChristine A WellsBrenda GibsonKaren KeeshanPublished in: Nature communications (2018)
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.
Keyphrases
- acute myeloid leukemia
- bone marrow
- allogeneic hematopoietic stem cell transplantation
- induced apoptosis
- intensive care unit
- emergency department
- liver failure
- young adults
- cell cycle arrest
- respiratory failure
- signaling pathway
- mesenchymal stem cells
- genome wide
- squamous cell carcinoma
- stem cells
- drug induced
- oxidative stress
- middle aged
- risk assessment
- cell proliferation
- immune response
- childhood cancer
- endoplasmic reticulum stress
- aortic dissection
- extracorporeal membrane oxygenation
- dna methylation
- acute respiratory distress syndrome
- pi k akt