|
|
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.
 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?
This article has been cited by other articles:
|
|
|
|
 
M. Germeshausen, M. Grudzien, C. Zeidler, H. Abdollahpour, S. Yetgin, N. Rezaei, M. Ballmaier, B. Grimbacher, K. Welte, and C. Klein
Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype associations
Blood,
May 15, 2008;
111(10):
4954 - 4957.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Badolato, M. Donini, G. Savoldi, and S. Dusi
Response: ELA2 genotype-phenotype correlation to be expected in patients with severe congenital neutropenia
Blood,
October 1, 2007;
110(7):
2773 - 2774.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-L. Casanova and L. Abel
Primary Immunodeficiencies: A Field in Its Infancy
Science,
August 3, 2007;
317(5838):
617 - 619.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. P. Alter
Diagnosis, Genetics, and Management of Inherited Bone Marrow Failure Syndromes
Hematology,
January 1, 2007;
2007(1):
29 - 39.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
