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

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Title: Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space
Authors: Lo Celso, C
Akinduro, O
Weber, TS
Haltalli, MLR
Ruivo, N
Duarte, D
Rashidi, NM
Hawkins, ED
Duffy, KR
Item Type: Journal Article
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.
Issue Date: 6-Feb-2018
Date of Acceptance: 24-Nov-2017
URI: http://hdl.handle.net/10044/1/53905
DOI: 10.1038/s41467-017-02376-5
ISSN: 2041-1723
Publisher: Nature Publishing Group
Start Page: 1
End Page: 12
Journal / Book Title: Nature Communications
Volume: 9
Copyright Statement: 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
Sponsor/Funder: Cancer Research UK
Commission of the European Communities
European Hematology Association
Wellcome Trust
Blood Cancer UK
Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: 11831
337066
n/a
105398/Z/14/Z
15031
BB/L023776/1
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CELLS IN-VIVO
STEM-CELLS
GERMINAL CENTER
SELF-RENEWAL
MULTIPOTENT PROGENITORS
CYCLE
DIFFERENTIATION
KINETICS
IDENTIFICATION
HETEROGENEITY
Animals
Bone Marrow
CD48 Antigen
Cell Count
Cell Proliferation
Female
Hematopoiesis
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Leukemia, Experimental
Leukemia, Myeloid, Acute
Mice, Inbred C57BL
Mice, Transgenic
S Phase
Hematopoietic Stem Cells
Bone Marrow
Animals
Mice, Inbred C57BL
Mice, Transgenic
Leukemia, Experimental
Hematopoietic Stem Cell Transplantation
Cell Count
S Phase
Hematopoiesis
Cell Proliferation
Female
Leukemia, Myeloid, Acute
CD48 Antigen
Publication Status: Published
Article Number: 519
Online Publication Date: 2018-02-06
Appears in Collections:Faculty of Natural Sciences