title: Congenital and acquired neutropenia.
abstract: Our understanding of the pathogenesis of congenital and acquired neutropenia is rapidly evolving. New ground-breaking observations have identified the genes responsible for many of the congenital neutropenia syndromes and are also providing new insights into normal neutrophil commitment and differentiation. Acquired neutropenia remains a poorly understood syndrome, although new insights into its pathogenesis are also emerging, especially with regard to subsets of immune neutropenia. In Section I, Dr. Marshall Horwitz reviews the current understanding of the genetic basis, molecular pathology, and approaches to treatment of congenital neutropenia and cyclic hematopoiesis. Mutations in the ELA2 gene, which encodes for neutrophil elastase, cause cyclic hematopoiesis. ELA2 mutations are also the most common cause of congenital neutropenia, where their presence may equate with a more severe clinical course and higher frequency of leukemic progression. Emerging evidence indicates interrelatedness with Hermansky Pudlak syndrome and other disorders of neutrophil and platelet granules. In Section II, Dr. Nancy Berliner presents an overview of the clinical approach to the evaluation and treatment of acquired neutropenia. This includes a review of the pathogenesis of primary and secondary immune neutropenia, drug-induced neutropenia, and non-immune chronic idiopathic neutropenia of adults. Studies used to evaluate patients for potential immune neutropenia are reviewed. Management issues, especially the use of granulocyte colony-stimulating factor (G-CSF), are discussed. In Section III, Dr. Thomas Loughran, Jr., reviews the pathogenesis and clinical manifestations of large granular lymphocyte (LGL) leukemia. Possible mechanisms of neutropenia are discussed. In particular, discussion focuses on the relationship between LGL leukemia, rheumatoid disease, and Felty's syndrome, and the complex interplay of defects in neutrophil production, distribution, destruction, and apoptosis that underly the development of neutropenia in those syndromes.
authors.affiliation: Yale University School of Medicine, Section of Hematology, New Haven, CT 06510, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Berliner
authors.forename: Marshall
authors.initials: M
authors.lastname: Horwitz
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Loughran
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D005258:Felty Syndrome / Q000150:complications; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D015458:Leukemia, T-Cell / Q000150:complications; D019272:Leukocyte Elastase / Q000235:genetics; D009154:Mutation / Q000235:genetics / Q000276:immunology; D009503:Neutropenia / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D019272:Leukocyte Elastase