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

Author

Listed:
  • Shahzya Chaudhury

    (University of Glasgow
    Royal Hospital for Children)

  • Caitríona O’Connor

    (University of Glasgow)

  • Ana Cañete

    (University of Glasgow)

  • Joana Bittencourt-Silvestre

    (University of Glasgow)

  • Evgenia Sarrou

    (University of Glasgow)

  • Áine Prendergast

    (University of Glasgow)

  • Jarny Choi

    (The University of Melbourne)

  • Pamela Johnston

    (University of Glasgow)

  • Christine A. Wells

    (The University of Melbourne)

  • Brenda Gibson

    (Royal Hospital for Children)

  • Karen Keeshan

    (University of Glasgow)

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.

Suggested Citation

  • Shahzya Chaudhury & Caitríona O’Connor & Ana Cañete & Joana Bittencourt-Silvestre & Evgenia Sarrou & Áine Prendergast & Jarny Choi & Pamela Johnston & Christine A. Wells & Brenda Gibson & Karen Keesha, 2018. "Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07584-1
    DOI: 10.1038/s41467-018-07584-1
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    Cited by:

    1. Hope Mumme & Beena E. Thomas & Swati S. Bhasin & Upaasana Krishnan & Bhakti Dwivedi & Pruthvi Perumalla & Debasree Sarkar & Gulay B. Ulukaya & Himalee S. Sabnis & Sunita I. Park & Deborah DeRyckere & , 2023. "Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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