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Leukaemia cell of origin identified by chromatin landscape of bulk tumour cells

Author

Listed:
  • Joshy George

    (The Jackson Laboratory for Genomic Medicine)

  • Asli Uyar

    (The Jackson Laboratory for Genomic Medicine)

  • Kira Young

    (The Jackson Laboratory for Mammalian Genetics)

  • Lauren Kuffler

    (The Jackson Laboratory for Mammalian Genetics)

  • Kaiden Waldron-Francis

    (The Jackson Laboratory for Mammalian Genetics)

  • Eladio Marquez

    (The Jackson Laboratory for Genomic Medicine)

  • Duygu Ucar

    (The Jackson Laboratory for Genomic Medicine)

  • Jennifer J. Trowbridge

    (The Jackson Laboratory for Mammalian Genetics)

Abstract

The precise identity of a tumour’s cell of origin can influence disease prognosis and outcome. Methods to reliably define tumour cell of origin from primary, bulk tumour cell samples has been a challenge. Here we use a well-defined model of MLL-rearranged acute myeloid leukaemia (AML) to demonstrate that transforming haematopoietic stem cells (HSCs) and multipotent progenitors results in more aggressive AML than transforming committed progenitor cells. Transcriptome profiling reveals a gene expression signature broadly distinguishing stem cell-derived versus progenitor cell-derived AML, including genes involved in immune escape, extravasation and small GTPase signal transduction. However, whole-genome profiling of open chromatin reveals precise and robust biomarkers reflecting each cell of origin tested, from bulk AML tumour cell sampling. We find that bulk AML tumour cells exhibit distinct open chromatin loci that reflect the transformed cell of origin and suggest that open chromatin patterns may be leveraged as prognostic signatures in human AML.

Suggested Citation

  • Joshy George & Asli Uyar & Kira Young & Lauren Kuffler & Kaiden Waldron-Francis & Eladio Marquez & Duygu Ucar & Jennifer J. Trowbridge, 2016. "Leukaemia cell of origin identified by chromatin landscape of bulk tumour cells," Nature Communications, Nature, vol. 7(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12166
    DOI: 10.1038/ncomms12166
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