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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4283-4287. Prepublished online as a Blood First Edition Paper on August 31, 2006; DOI 10.1182/blood-2006-03-007997. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-007997v1 108/13/4283    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 Si, Y. Articles by Clapp, D. W. Search for Related Content PubMed PubMed Citation Articles by Si, Y. Articles by Clapp, D. W. Related Collections Hematopoiesis and Stem Cells Immunobiology Transplantation Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Continuous in vivo infusion of interferon-gamma (IFN-) enhances engraftment of syngeneic wild-type cells in Fanca–/– and Fancg–/– mice Yue Si, Samantha Ciccone, Feng-Chun Yang, Jin Yuan, Daisy Zeng, Shi Chen, Henri J. van de Vrugt, John Critser, Fre Arwert, Laura S. Haneline, and D. Wade Clapp From the Department of Microbiology and Immunology and the Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis; the Department of Laboratory Pathology, Comparative Medicine Center, University of Missouri, St Louis; and the Department of Clinical Genetics and Human Genetics, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands. Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow (BM) failure and cancer susceptibility. Identification of the cDNAs of FA complementation types allows the potential of using gene transfer technology to introduce functional cDNAs as transgenes into autologous stem cells and provide a cure for the BM failure in FA patients. However, strategies to enhance the mobilization, transduction, and engraftment of exogenous stem cells are required to optimize efficacy prior to widespread clinical use. Hypersensitivity of Fancc–/– cells to interferon-gamma (IFN-), a nongenotoxic immune-regulatory cytokine, enhances engraftment of syngeneic wild-type (WT) cells in Fancc–/– mice. However, whether this phenotype is of broad relevance in other FA complementation groups is unresolved. Here we show that primitive and mature myeloid progenitors in Fanca–/– and Fancg–/– mice are hypersensitive to IFN- and that in vivo infusion of IFN- at clinically relevant concentrations was sufficient to allow consistent long-term engraftment of isogenic WT repopulating stem cells. Given that FANCA, FANCC, and FANCG complementation groups account for more than 90% of all FA patients, these data provide evidence that IFN- conditioning may be a useful nongenotoxic strategy for myelopreparation in FA patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Li, S. Chen, J. Yuan, Y. Yang, J. Li, J. Ma, X. Wu, M. Freund, K. Pollok, H. Hanenberg, et al. Mesenchymal stem/progenitor cells promote the reconstitution of exogenous hematopoietic stem cells in Fancg-/- mice in vivo Blood, March 5, 2009; 113(10): 2342 - 2351. [Abstract] [Full Text] [PDF] P. Rio, N. W. Meza, A. Gonzalez-Murillo, S. Navarro, L. Alvarez, J. Surralles, M. Castella, G. Guenechea, J. C. Segovia, H. Hanenberg, et al. In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1 Blood, December 15, 2008; 112(13): 4853 - 4861. [Abstract] [Full Text] [PDF] Y. Si, A. C. Pulliam, Y. Linka, S. Ciccone, C. Leurs, J. Yuan, O. Eckermann, S. Fruehauf, S. Mooney, H. Hanenberg, et al. Overnight transduction with foamyviral vectors restores the long-term repopulating activity of Fancc-/- stem cells Blood, December 1, 2008; 112(12): 4458 - 4465. [Abstract] [Full Text] [PDF] X. Zhang, D. P. Sejas, Y. Qiu, D. A. Williams, and Q. Pang Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescence J. Cell Sci., May 1, 2007; 120(9): 1572 - 1583. [Abstract] [Full Text] [PDF] D. P. Sejas, R. Rani, Y. Qiu, X. Zhang, S. R. Fagerlie, H. Nakano, D. A. Williams, and Q. Pang Inflammatory Reactive Oxygen Species-Mediated Hemopoietic Suppression in Fancc-Deficient Mice J. Immunol., April 15, 2007; 178(8): 5277 - 5287. [Abstract] [Full Text] [PDF]

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