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Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space

Author

Listed:
  • O. Akinduro

    (Imperial College London)

  • T. S. Weber

    (Maynooth University
    The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • H. Ang

    (Imperial College London)

  • M. L. R. Haltalli

    (Imperial College London)

  • N. Ruivo

    (Imperial College London)

  • D. Duarte

    (Imperial College London
    The Francis Crick Institute)

  • N. M. Rashidi

    (Imperial College London)

  • E. D. Hawkins

    (Imperial College London
    The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • K. R. Duffy

    (Maynooth University)

  • C. Lo Celso

    (Imperial College London
    The Francis Crick Institute)

Abstract

Leukaemia progressively invades bone marrow (BM), outcompeting healthy haematopoiesis by mechanisms that are not fully understood. Combining cell number measurements with a short-timescale dual pulse labelling method, we simultaneously determine the proliferation dynamics of primitive haematopoietic compartments and acute myeloid leukaemia (AML). We observe an unchanging proportion of AML cells entering S phase per hour throughout disease progression, with substantial BM egress at high levels of infiltration. For healthy haematopoiesis, we find haematopoietic stem cells (HSCs) make a significant contribution to cell production, but we phenotypically identify a quiescent subpopulation with enhanced engraftment ability. During AML progression, we observe that multipotent progenitors maintain a constant proportion entering S phase per hour, despite a dramatic decrease in the overall population size. Primitive populations are lost from BM with kinetics that are consistent with ousting irrespective of cell cycle state, with the exception of the quiescent HSC subpopulation, which is more resistant to elimination.

Suggested Citation

  • O. Akinduro & T. S. Weber & H. Ang & M. L. R. Haltalli & N. Ruivo & D. Duarte & N. M. Rashidi & E. D. Hawkins & K. R. Duffy & C. Lo Celso, 2018. "Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02376-5
    DOI: 10.1038/s41467-017-02376-5
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    Cited by:

    1. Georgia K. Atkin-Smith & Jascinta P. Santavanond & Amanda Light & Joel S. Rimes & Andre L. Samson & Jeremy Er & Joy Liu & Darryl N. Johnson & Mélanie Le Page & Pradeep Rajasekhar & Raymond K. H. Yip &, 2024. "In situ visualization of endothelial cell-derived extracellular vesicle formation in steady state and malignant conditions," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Mina N. F. Morcos & Congxin Li & Clara M. Munz & Alessandro Greco & Nicole Dressel & Susanne Reinhardt & Katrin Sameith & Andreas Dahl & Nils B. Becker & Axel Roers & Thomas Höfer & Alexander Gerbaule, 2022. "Fate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Narasaiah Kovuru & Makiko Mochizuki-Kashio & Theresa Menna & Greer Jeffrey & Yuning Hong & Young me Yoon & Zhe Zhang & Peter Kurre, 2024. "Deregulated protein homeostasis constrains fetal hematopoietic stem cell pool expansion in Fanconi anemia," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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