title: Molecular basis and therapy of disorders associated with chronic neutropenia.
abstract: There have been many recent advances in our understanding of the molecular basis of neutropenia disorders, primarily through advances in genetic analysis of inherited disorders. Molecular and cellular studies now suggest that accelerated apoptosis of neutrophil precursors in the bone marrow is the common pathophysiologic mechanism. Severe congenital neutropenia and cyclic neutropenia, both usually inherited as autosomal-dominant disorders, are caused by mutations in the neutrophil elastase gene. Myelokathexis is attributed to the downregulation of the bcl-x protein, but the genetic basis is not yet known. The genes for several diseases with more complex phenotypes (eg, glycogen storage disease type 1b, Chediak-Higashi syndrome, Shwachman-Diamond syndrome, dyskeratosis congenita, Griscelli syndrome, Barth syndrome, and Wiskott-Aldrich syndrome) have all been identified recently. The molecular mechanisms for most acquired disorders causing neutropenia (eg, idiopathic neutropenia, pure white-cell aplasia, myelodysplasia, and aplastic anemia) are not yet known. Granulocyte colony stimulating factor (G-CSF) is effective treatment for several of these conditions. Through better understanding of these disorders, we anticipate that better treatments will be found in the future.
authors.affiliation: Department of Medicine, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356422, Seattle, WA 98195, USA. stevs@u.washington.edu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Stein
authors.forename: David C
authors.initials: DC
authors.lastname: Dale
mesh_terms: D001853:Bone Marrow / Q000473:pathology; D002609:Chediak-Higashi Syndrome / Q000235:genetics; D002908:Chronic Disease; D019871:Dyskeratosis Congenita / Q000235:genetics; D010188:Exocrine Pancreatic Insufficiency / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D005953:Glycogen Storage Disease Type I / Q000235:genetics; D006801:Humans; D017496:Hypopigmentation / Q000235:genetics; D009503:Neutropenia / Q000151:congenital* / Q000235:genetics*; D009504:Neutrophils / Q000473:pathology; D010507:Periodicity; D013577:Syndrome; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics