title: Understanding chronic neutropenia: life is short.
abstract: The pathophysiological mechanisms underlying chronic neutropenia are extensive, varying from haematopoietic stem cell disorders resulting in defective neutrophil production, to accelerated apoptosis of neutrophil progenitors or circulating mature neutrophils. While the knowledge concerning genetic defects associated with congenital neutropenia or bone marrow failure is increasing rapidly, the functional role and consequences of these genetic alterations is often not well understood. In addition, there is a large group of diseases, including primary immunodeficiencies and metabolic diseases, in which chronic neutropenia is one of the symptoms, while there is no clear bone marrow pathology or haematopoietic stem cell dysfunction. Altogether, these disease entities illustrate the complexity of normal neutrophil development, the functional role of the (bone marrow) microenvironment and the increased propensity to undergo apoptosis, which is typical for neutrophils. The large variety of disorders associated with chronic neutropenia makes classification almost impossible and possibly not desirable, based on the clinical phenotypes. However, a better understanding of the regulation of normal myeloid differentiation and neutrophil development is of great importance in the diagnostic evaluation of unexplained chronic neutropenia. In this review we propose insights in the pathophysiology of chronic neutropenia in the context of the functional role of key players during normal neutrophil development, neutrophil release and neutrophil survival.
authors.affiliation: Department of Paediatric Haematology and Stem Cell Transplantation, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Marije
authors.initials: M
authors.lastname: Bartels
authors.affiliation: Department of Paediatric Haematology and Stem Cell Transplantation, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Kate
authors.initials: K
authors.lastname: Murphy
authors.affiliation: Department of Paediatric Haematology and Stem Cell Transplantation, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Ester
authors.initials: E
authors.lastname: Rieter
authors.affiliation: Department of Paediatric Haematology and Stem Cell Transplantation, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Marrie
authors.initials: M
authors.lastname: Bruin
mesh_terms: D001854:Bone Marrow Cells / Q000473:pathology; D002454:Cell Differentiation; D002908:Chronic Disease; D000080984:Congenital Bone Marrow Failure Syndromes; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D009503:Neutropenia / Q000151:congenital / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology
keywords: bone marrow; genetic defects; neutropenia; neutrophils