Journal article

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

O Akinduro, TS Weber, H Ang, MLR Haltalli, N Ruivo, D Duarte, NM Rashidi, ED Hawkins, KR Duffy, C Lo Celso

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2018

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 en..

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Grants

Awarded by CRUK


Awarded by ERC


Awarded by BBSRC


Awarded by Science Foundation Ireland


Awarded by Wellcome Trust


Awarded by FCT/GABBA


Awarded by Biotechnology and Biological Sciences Research Council


Awarded by Cancer Research UK


Funding Acknowledgements

We thank Steve Lane (QIMR Berghofer, Brisbane) for input on establishing the MLL-AF9 AML experimental model; Jane Srivastava, Catherine Simpson and Jess Rowley for support from the ICL Department of Life Sciences Flow cytometry facility; ICL CBS and Crick BRF staff for mouse husbandry; and Peter O'Donovan for critical input on the manuscript. This work was funded by CRUK (grant No. C36195/A1183 to C.L.C.), ERC (grant No. 337066 to C.L.C.), BBSRC (grant No. BB/I004033/1 to C.L.C.), Science Foundation Ireland (grant No. 12IP1263 to K.R.D.), Wellcome Trust (fellowship 105398/Z/14/Z to M.L.H.) and FCT/GABBA (fellowship SFRH/BD/52195/2013 to D.D.).