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

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    Author
    Akinduro, O; Weber, TS; Ang, H; Haltalli, MLR; Ruivo, N; Duarte, D; Rashidi, NM; Hawkins, ED; Duffy, KR; Lo Celso, C
    Date
    2018-02-06
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Hawkins, Edwin; Weber, Tom
    Affiliation
    Medical Biology (W.E.H.I.)
    Metadata
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    Document Type
    Journal Article
    Citations
    Akinduro, O., Weber, T. S., Ang, H., Haltalli, M. L. R., Ruivo, N., Duarte, D., Rashidi, N. M., Hawkins, E. D., Duffy, K. R. & Lo Celso, C. (2018). Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space. NATURE COMMUNICATIONS, 9 (1), https://doi.org/10.1038/s41467-017-02376-5.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256015
    DOI
    10.1038/s41467-017-02376-5
    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.

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