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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5234-5237. Prepublished online as a Blood First Edition Paper on February 20, 2007; DOI 10.1182/blood-2006-12-063495. This Article Full Text (PDF) Supplemental Methods All Versions of this Article: blood-2006-12-063495v1 109/12/5234    most recent Alert me when this article is cited Alert me if a correction is posted 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 Solomou, E. E Articles by Young, N. S Search for Related Content PubMed PubMed Citation Articles by Solomou, E. E Articles by Young, N. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 18, 2006 Accepted February 14, 2007 Perforin gene mutations in patients with acquired aplastic anemia Elena E Solomou*, Federica Gibellini, Brian Stewart, Daniela Malide, Maria Berg, Valeria Visconte, Spencer Green, Richard Childs, Stephen J Chanock, and Neal S Young Hematology Branch, NHLBI, NIH, Bethesda, MD, United States Pediatric Oncology Branch, NCI, NIH, Bethesda, MD, United States Light microscopy core facility, NHLBI, NIH, Bethesda, MD, United States * Corresponding author; email: solomoue{at}nhlbi.nih.gov. Perforin is a cytolytic protein expressed mainly in activated cytotoxic lymphocytes and natural-killer cells. Inherited perforin mutations account for 20-40% of familial hemophagocytic lymphohistiocytosis, a fatal disease of early childhood characterized by absence of functional perforin. Aplastic anemia, the paradigm of immune mediated bone marrow failure syndromes, is characterized by hematopoietic stem cell destruction by activated T-cells and Th1-cytokines. We examined whether mutations in the perforin gene occurred in acquired aplastic anemia. Three nonsynonymous PRF1 mutations among five unrelated patients were observed. Four out of five patients with the mutations showed some hemophagocytosis in the bone marrow at diagnosis. Perforin protein levels in these patients were very low or absent, and perforin granules were completely absent. NK-cell cytotoxicity from these patients was significantly decreased. Our data suggest that PRF1 genetic alterations help explain the aberrant proliferation and activation of cytotoxic T-cells and may represent genetic risk factors for bone marrow failure. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. O. Omokaro, M. J. Desierto, M. A. Eckhaus, F. M. Ellison, J. Chen, and N. S. Young Lymphocytes with Aberrant Expression of Fas or Fas Ligand Attenuate Immune Bone Marrow Failure in a Mouse Model J. Immunol., March 15, 2009; 182(6): 3414 - 3422. [Abstract] [Full Text] [PDF] A Trizzino, U z. Stadt, I Ueda, K Risma, G Janka, E Ishii, K Beutel, J Sumegi, S Cannella, D Pende, et al. Genotype phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations J. Med. Genet., January 1, 2008; 45(1): 15 - 21. [Abstract] [Full Text] [PDF] E. E. Solomou, K. Rezvani, S. Mielke, D. Malide, K. Keyvanfar, V. Visconte, S. Kajigaya, A. J. Barrett, and N. S. Young Deficient CD4+ CD25+ FOXP3+ T regulatory cells in acquired aplastic anemia Blood, September 1, 2007; 110(5): 1603 - 1606. [Abstract] [Full Text] [PDF]

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