Journal article
T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments
ED Hawkins, D Duarte, O Akinduro, RA Khorshed, D Passaro, M Nowicka, L Straszkowski, MK Scott, S Rothery, N Ruivo, K Foster, M Waibel, RW Johnstone, SJ Harrison, DA Westerman, H Quach, J Gribben, MD Robinson, LE Purton, D Bonnet Show all
Nature | NATURE PUBLISHING GROUP | Published : 2016
DOI: 10.1038/nature19801
Abstract
It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions a..
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Awarded by European Hematology Association
Funding Acknowledgements
E.D.H. was supported by a fellowship from the European Haematology Association and an RD Wright Career fellowship from the National Health and Medical Research Council of Australia (NHMRC) as well as a project grant from Bloodwise (12033). D.D. was supported by the GABBA PhD program (FCT fellowship SFRH/BD/52195/2013). L.E.P. was supported by a National Health and Medical Research Council of Australia Senior Research Fellowship. H.Q. is supported by Victorian Cancer Agency Early Career Seed Grant. D.B., D.P. and K.F. were funded by Cancer Research UK (CRUK) and the Francis Crick Institute. C.L.C. was funded by Bloodwise (12033), Human Frontier Science Program (RGP0051/2011), CRUK (036195/41183), Biotechnology and Biological Sciences Research Council (BB/1004033/1) Kay Kendall Leukaemia Fund (KKL460) and the European Research Council (337066). We are grateful to M. Spitaler, D. Keller and L. Carlin for support with imaging. We also thank S. Piperelis, E. Ibarguen, W. Steel and H. Goyal for logistical help; A. Ivan for support from the genomics facility; J. Srivastava and C. Simpson for support from the flow cytometry facility; M. Wall for her advice on the human cytogenetics; D. Ibanez for access to software; H. Fleming, V. Greco, R. E. Sinden, S. Mostowy and P O'Donovan for critical feedback on the manuscript.