Progenitor cell self-renewal and cyclic neutropenia

David M Dingli, T. Antal, A. Traulsen, J. M. Pacheco

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)330-338
Number of pages9
JournalCell Proliferation
Volume42
Issue number3
DOIs
StatePublished - Jun 2009

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Granulocyte Colony-Stimulating Factor
Stem Cells
Hematopoiesis
Neutrophils
Leukocyte Elastase
Mutation
Inborn Genetic Diseases
Cell Count
Bone Marrow
Cyclic neutropenia
Cell Self Renewal
Infection
Genes
Therapeutics

ASJC Scopus subject areas

  • Cell Biology

Cite this

Progenitor cell self-renewal and cyclic neutropenia. / Dingli, David M; Antal, T.; Traulsen, A.; Pacheco, J. M.

In: Cell Proliferation, Vol. 42, No. 3, 06.2009, p. 330-338.

Research output: Contribution to journalArticle

Dingli, David M ; Antal, T. ; Traulsen, A. ; Pacheco, J. M. / Progenitor cell self-renewal and cyclic neutropenia. In: Cell Proliferation. 2009 ; Vol. 42, No. 3. pp. 330-338.
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