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          Institute: MPI für Evolutionsbiologie     Collection: Evolutionary ecology     Display Documents



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ID: 430629.0, MPI für Evolutionsbiologie / Evolutionary ecology
Progenitor cell self-renewal and cyclic neutropenia
Authors:Dingli, D.; Antal, T.; Traulsen, A.; Pacheco, J. M.
Language:English
Date of Publication (YYYY-MM-DD):2009-06
Title of Journal:Cell Proliferation
Journal Abbrev.:Cell Prolif.
Volume:42
Issue / Number:3
Start Page:330
End Page:338
Review Status:not specified
Audience:Not Specified
Abstract / Description:Objectives: Cyclic neutropenia (CN) is a rare genetic disorder where patients experience regular cycling of numbers of neutrophils and various other haematopoietic lineages. The nadir in neutrophil count is the main source of problems due to risk of life-threatening infections. Patients with CN benefit from granulocyte colony stimulating factor therapy, although cycling persists. Mutations in neutrophil elastase gene (ELA2) have been found in more than half of patients with CN. However, neither connection between phenotypic expression of ELA2 and CN nor the mechanism of cycling is known.

Materials and methods: Recently, a multicompartment model of haematopoiesis that couples stem cell replication with marrow output has been proposed. In the following, we couple this model of haematopoiesis with a linear feedback mechanism via G-CSF.

Results: We propose that the phenotypic effect of ELA2 mutations leads to reduction in self-renewal of granulocytic progenitors. The body responds by overall relative increase of G-CSF and increasing progenitor cell self-renewal, leading to cell count cycling.

Conclusion: The model is compatible with available experimental data and makes testable predictions.
External Publication Status:published
Document Type:Article
Affiliations:MPI für Evolutionsbiologie/Abt. Evolutionsökologie
MPI für Evolutionsbiologie/AG Evolutionstheorie
External Affiliations:Division of Hematology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA; Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, USA; Applications of Theoretical Physics-Group, Center for Theoretical and Computational Physics & Department of Physics, Faculty of Science, Lisbon, Portugal
Identifiers:ISSN:0960-7722 (print) [ID-No:1]
ISSN:1365-2184 (online) [ID-No:2]
DOI:10.1111/j.1365-2184.2009.00598.x [ID-No:3]
LOCALID:2699/S 39000 [Listen-Nummer/S-Nummer]
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