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


    Akinduro, Olufolake and Weber, Tom S. and Ang, Heather and Haltalli, Myriam and Ruivo, Nicola and Duarte, Delfim and Rashidi, N.M. and Hawkins, Edwin D. and Duffy, Ken R. and Lo Celso, Christina (2018) Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space. Nature Communications, 9 (519). ISSN 2041-1723

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    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.

    Item Type: Article
    Additional Information: Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. © The Author(s) 2018
    Keywords: Proliferation dynamics; acute myeloid leukaemia; haematopoietic progenitors; bone marrow space;
    Academic Unit: Faculty of Science and Engineering > Research Institutes > Hamilton Institute
    Item ID: 10166
    Identification Number: https://doi.org/10.1038/s41467-017-02376-5
    Depositing User: Dr Ken Duffy
    Date Deposited: 01 Nov 2018 16:30
    Journal or Publication Title: Nature Communications
    Publisher: Nature Research
    Refereed: Yes
    Funders: CRUK, European Research Council (ERC), Science Foundation Ireland, Wellcome Tust, FCT/GABBA
    URI:

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