Show simple item record

dc.contributor.authorDinh, Khanh N.
Corey, Seth J.
Kimmel, Marek
dc.date.accessioned 2020-10-21T18:16:22Z
dc.date.available 2020-10-21T18:16:22Z
dc.date.issued 2020
dc.identifier.citation Dinh, Khanh N., Corey, Seth J. and Kimmel, Marek. "Application of the Moran Model in Estimating Selection Coefficient of Mutated CSF3R Clones in the Evolution of Severe Congenital Neutropenia to Myeloid Neoplasia." Frontiers in Physiology, 11, (2020) Frontiers: https://doi.org/10.3389/fphys.2020.00806.
dc.identifier.urihttps://hdl.handle.net/1911/109442
dc.description.abstract Bone marrow failure (BMF) syndromes, such as severe congenital neutropenia (SCN) are leukemia predisposition syndromes. We focus here on the transition from SCN to pre-leukemic myelodysplastic syndrome (MDS). Stochastic mathematical models have been conceived that attempt to explain the transition of SCN to MDS, in the most parsimonious way, using extensions of standard processes of population genetics and population dynamics, such as the branching and the Moran processes. We previously presented a hypothesis of the SCN to MDS transition, which involves directional selection and recurrent mutation, to explain the distribution of ages at onset of MDS or AML. Based on experimental and clinical data and a model of human hematopoiesis, a range of probable values of the selection coefficient s and mutation rate μ have been determined. These estimates lead to predictions of the age at onset of MDS or AML, which are consistent with the clinical data. In the current paper, based on data extracted from published literature, we seek to provide an independent validation of these estimates. We proceed with two purposes in mind: (i) to determine the ballpark estimates of the selection coefficients and verify their consistency with those previously obtained and (ii) to provide possible insight into the role of recurrent mutations of the G-CSF receptor in the SCN to MDS transition.
dc.language.iso eng
dc.publisher Frontiers
dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.title Application of the Moran Model in Estimating Selection Coefficient of Mutated CSF3R Clones in the Evolution of Severe Congenital Neutropenia to Myeloid Neoplasia
dc.type Journal article
dc.citation.journalTitle Frontiers in Physiology
dc.subject.keywordClinical data
G-CSF receptor (G-CSFR)
Moran model
Myeloid neoplasia
Recurrent mutation
dc.citation.volumeNumber 11
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.3389/fphys.2020.00806
dc.type.publication publisher version


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record