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  Progenitor cell self-renewal and cyclic neutropenia

Dingli, D., Antal, T., Traulsen, A., & Pacheco, J. M. (2009). Progenitor cell self-renewal and cyclic neutropenia. Cell Proliferation, 42(3), 330-338. doi:10.1111/j.1365-2184.2009.00598.x.

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Dingli_CP_2009.pdf (Verlagsversion), 583KB
 
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 Urheber:
Dingli, D., Autor
Antal, T., Autor
Traulsen, A.1, 2, Autor           
Pacheco, J. M., Autor
Affiliations:
1Department Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445634              
2Research Group Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445641              

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 Zusammenfassung: 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.

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Sprache(n): eng - English
 Datum: 2009-06
 Publikationsstatus: Erschienen
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 Identifikatoren: eDoc: 430629
DOI: 10.1111/j.1365-2184.2009.00598.x
Anderer: 2699/S 39000
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Titel: Cell Proliferation
  Alternativer Titel : Cell Prolif.
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 42 (3) Artikelnummer: - Start- / Endseite: 330 - 338 Identifikator: ISSN: 0960-7722 (print)
ISSN: 1365-2184 (online)