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

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Akinduro, O (Author) Other; Weber, TS (Author) Other; Ang, H (Author) Other; Haltalli, MLR (Author) Other; Ruivo, N (Author) Other; Duarte, D (Author) FMUP; Rashidi, NM (Author) Other; Hawkins, ED (Author) Other; Duffy, KR (Author) Other; Lo Celso, C (Author) Other

Journal

Title: Nature Communications

Vol. 9 No. 1

ISSN: 2041-1723

Publisher: Springer Nature

Indexing

Scopus - 38 Citations

Other information

Authenticus ID: P-00T-90V

DOI: 10.1038/s41467-017-02376-5

Abstract (EN): 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. © 2018 The Author(s).

Language: English

Type (Professor's evaluation): Scientific