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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1817-1824. Prepublished online as a Blood First Edition Paper on November 14, 2006; DOI 10.1182/blood-2006-08-019166. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-08-019166v1 blood-2006-08-019166v2 109/5/1817    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Horwitz, M. S. Articles by Salipante, S. J. Search for Related Content PubMed PubMed Citation Articles by Horwitz, M. S. Articles by Salipante, S. J. Related Collections Hematopoiesis and Stem Cells Phagocytes Review Articles Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  REVIEW ARTICLE Neutrophil elastase in cyclic and severe congenital neutropenia Marshall S. Horwitz1, Zhijun Duan1, Brice Korkmaz1, Hu-Hui Lee1, Matthew E. Mealiffe1, and Stephen J. Salipante2 1 Division of Medical Genetics, Department of Medicine, and 2 Department of Genome Sciences, University of Washington School of Medicine, Seattle Mutations in ELA2 encoding the neutrophil granule protease, neutrophil elastase (NE), are the major cause of the 2 main forms of hereditary neutropenia, cyclic neutropenia and severe congenital neutropenia (SCN). Genetic evaluation of other forms of neutropenia in humans and model organisms has helped to illuminate the role of NE. A canine form of cyclic neutropenia corresponds to human Hermansky-Pudlak syndrome type 2 (HPS2) and results from mutations in AP3B1 encoding a subunit of a complex involved in the subcellular trafficking of vesicular cargo proteins (among which NE appears to be one). Rare cases of SCN are attributable to mutations in the transcriptional repressor Gfi1 (among whose regulatory targets also include ELA2). The ultimate biochemical consequences of the mutations are not yet known, however. Gene targeting of ELA2 has thus far failed to recapitulate neutropenia in mice. The cycling phenomenon and origins of leukemic transformation in SCN remain puzzling. Nevertheless, mutations in all 3 genes are capable of causing the mislocalization of NE and may also induce the unfolded protein response, suggesting that there might a convergent pathogenic mechanism focusing on NE. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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