A somatic evolutionary model of the dynamics of aneuploid cells during hematopoietic reconstitution.

Scientific Reports
Andrii I RozhokJames DeGregori

Abstract

Aneuploidy is a feature of many cancers. Recent studies demonstrate that in the hematopoietic stem and progenitor cell (HSPC) compartment aneuploid cells have reduced fitness and are efficiently purged from the bone marrow. However, early phases of hematopoietic reconstitution following bone marrow transplantation provide a window of opportunity whereby aneuploid cells rise in frequency, only to decline to basal levels thereafter. Here we demonstrate by Monte Carlo modeling that two mechanisms could underlie this aneuploidy peak: rapid expansion of the engrafted HSPC population and bone marrow microenvironment degradation caused by pre-transplantation radiation treatment. Both mechanisms reduce the strength of purifying selection acting in early post-transplantation bone marrow. We explore the contribution of other factors such as alterations in cell division rates that affect the strength of purifying selection, the balance of drift and selection imposed by the HSPC population size, and the mutation-selection balance dependent on the rate of aneuploidy generation per cell division. We propose a somatic evolutionary model for the dynamics of cells with aneuploidy or other fitness-reducing mutations during hematopoietic reconsti...Continue Reading

References

Mar 27, 1997·The New England Journal of Medicine·R E CurtisJ D Boice
Feb 26, 2000·Carcinogenesis·J B Little
Jun 23, 2004·Nature Genetics·Darren J BakerJan M van Deursen
Nov 19, 2004·Nature·Harith Rajagopalan, Christoph Lengauer
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Curtis J HenryJames DeGregori
Jan 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Xu CaoFrank J Frassica
Apr 19, 2011·Trends in Genetics : TIG·Subhajyoti De
Jan 25, 2012·Nature Reviews. Genetics·David J GordonDavid Pellman
Sep 14, 2012·Nature Reviews. Cancer·Josep V FormentStephen P Jackson
Dec 12, 2012·Genes & Development·Ana B OromendiaAngelika Amon
Dec 21, 2012·Journal of the Royal Society, Interface·Erica ManessoCarsten Peterson
Sep 13, 2013·Nature·Maddalena AdornoMichael F Clarke
Jan 17, 2014·Nature·Sean J Morrison, David T Scadden
Sep 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Kristin A KnouseAngelika Amon
Oct 9, 2014·Nature·Jianlong SunFernando D Camargo
Nov 27, 2014·The New England Journal of Medicine·Siddhartha JaiswalBenjamin L Ebert
Nov 27, 2014·The New England Journal of Medicine·Giulio GenoveseSteven A McCarroll
Feb 14, 2015·Cell·Guangbo ChenRong Li
Jun 16, 2015·Stem Cells International·Sharath P SasiDavid A Goukassian
Jul 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Andrii I Rozhok, James DeGregori
Jul 24, 2015·Nature Reviews. Molecular Cell Biology·Stefano Santaguida, Angelika Amon
Sep 25, 2015·Science Translational Medicine·Thomas McKerrell, George S Vassiliou
Nov 13, 2015·Proceedings of the National Academy of Sciences of the United States of America·Shaoping LingChung-I Wu
Nov 18, 2015·Nature Communications·Delphine GogendeauRenata Basto
Jan 13, 2016·Proceedings of the National Academy of Sciences of the United States of America·Andrii I RozhokJames DeGregori
Mar 8, 2016·Trends in Cancer·Kamil A LipinskiMarco Gerlinger
Jan 5, 2017·Cold Spring Harbor Perspectives in Medicine·Laurent Sansregret, Charles Swanton
Apr 26, 2017·Trends in Cancer·Andrii I Rozhok, James DeGregori
Oct 11, 2017·PLoS Computational Biology·Peter AshcroftSebastian Bonhoeffer
Oct 24, 2017·Cell·Iñigo MartincorenaPeter J Campbell
Apr 7, 2018·Cancer Cell·Alison M TaylorMatthew Meyerson
Dec 24, 2018·Journal of Theoretical Biology·Nils B BeckerThomas Höfer
Jan 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Rong LuIrving L Weissman
Apr 30, 2019·ELife·Andrii Rozhok, James DeGregori

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