Stochastic hypothesis of transition from inborn neutropenia to AML: interactions of cell population dynamics and population genetics

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dc.citation.journalTitleFrontiers in Oncologyen_US
dc.citation.volumeNumber3en_US
dc.contributor.authorKimmel, Mareken_US
dc.contributor.authorCorey, Sethen_US
dc.date.accessioned2013-06-28T18:05:33Zen_US
dc.date.available2013-06-28T18:05:33Zen_US
dc.date.issued2013en_US
dc.description.abstractWe present a stochastic model of driver mutations in the transition from severe congenital neutropenia to myelodysplastic syndrome to acute myeloid leukemia (AML). The model has the form of a multitype branching process. We derive equations for the distributions of the times to consecutive driver mutations and set up simulations involving a range of hypotheses regarding acceleration of the mutation rates in successive mutant clones. Our model reproduces the clinical distribution of times at diagnosis of secondary AML. Surprisingly, within the framework of our assumptions, stochasticity of the mutation process is incapable of explaining the spread of times at diagnosis of AML in this case; it is necessary to additionally assume a wide spread of proliferative parameters among disease cases. This finding is unexpected but generally consistent with the wide heterogeneity of characteristics of human cancers.en_US
dc.embargo.termsnoneen_US
dc.identifier.citationKimmel, Marek and Corey, Seth. "Stochastic hypothesis of transition from inborn neutropenia to AML: interactions of cell population dynamics and population genetics." <i>Frontiers in Oncology,</i> 3, (2013) Frontiers Media: http://dx.doi.org/10.3389/fonc.2013.00089.en_US
dc.identifier.doihttp://dx.doi.org/10.3389/fonc.2013.00089en_US
dc.identifier.urihttps://hdl.handle.net/1911/71486en_US
dc.language.isoengen_US
dc.publisherFrontiers Mediaen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/en_US
dc.subject.keywordsevere congenital neutropeniaen_US
dc.subject.keywordmyelodysplastic syndromeen_US
dc.subject.keywordacute myeloid leukemiaen_US
dc.subject.keywordbranching processen_US
dc.subject.keyworddriver mutationsen_US
dc.subject.keywordclonal evolutionen_US
dc.titleStochastic hypothesis of transition from inborn neutropenia to AML: interactions of cell population dynamics and population geneticsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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