Pathogenic mechanisms and clinical implications of congenital neutropenia syndromes

Hauck, Fabian und Klein, Christoph (Dezember 2013): Pathogenic mechanisms and clinical implications of congenital neutropenia syndromes. In: Current Opinion in Allergy and Clinical Immunology, Bd. 13, Nr. 6: S. 596-606

Abstract

Purpose of reviewThe purpose of this review is to summarize pathogenic mechanisms and clinical implications of the most illustrative genetic entities of congenital neutropenia syndromes.Recent findingsCongenital neutropenia comprise monogenetic entities with or without additional immunologic and extrahaematopoietic syndromatic features. Continuous careful explorations of known entities such as ELANE, GFI1, HAX1, G6PC3 deficiency and XLN help to define principles controlling differentiation and function of neutrophil granulocytes. Furthermore, the identification of novel genetic defects associated with congenital neutropenia, such as VPS45 deficiency, broadens our understanding of neutrophil biology. Pathogenic mechanisms imply protein and vesicle mistrafficking, endoplasmic reticulum stress, the unfolded protein response, destabilization of the mitochondrial membrane potential, disturbed energy metabolism, dysglycosylation and deregulated actin polymerization.SummaryAdvanced genetic and biochemical techniques have helped to expand our knowledge of congenital neutropenia syndromes. Known and novel genetic entities shed light on fundamental biological processes important for the homeostatis and functioning not only of the neutrophil granulocyte but as well of the entire haematopoietic system. Furthermore, treatment decisions become more tailored and might pave the road towards personalized molecular medicine.

• Dokumententyp: Zeitschriftenartikel
• Publikationsform: Publisher's Version
• Keywords: elastase neutrophil expressed; glucose 6 phosphatase catalytic subunit 3; growth factor independent 1 transcription repressor; haematopoietic cell specific LYN substrate 1 associated protein X-1; severe congenital neutropenia; vacuolar protein sorting 45 homolog; X-linked neutropenia
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1528-4050
• Ort: 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
• Allianz-/Nationallizenz: Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
• Sprache: Englisch