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Blood, 15 July 2007, Vol. 110, No. 2, pp. 719-726. Prepublished online as a Blood First Edition Paper on April 9, 2007; DOI 10.1182/blood-2007-01-068809. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-01-068809v1 110/2/719    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 Joslin, J. M. Articles by Le Beau, M. M. Search for Related Content PubMed PubMed Citation Articles by Joslin, J. M. Articles by Le Beau, M. M. Related Collections Neoplasia Oncogenes and Tumor Suppressors Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Haploinsufficiency of EGR1, a candidate gene in the del(5q), leads to the development of myeloid disorders John M. Joslin1, Anthony A. Fernald1, Thelma R. Tennant1, Elizabeth M. Davis1, Scott C. Kogan2, John Anastasi3, John D. Crispino4, and Michelle M. Le Beau1 1 Section of Hematology/Oncology and the Cancer Research Center, University of Chicago, IL; 2 Department of Laboratory Medicine, University of California at San Francisco; 3 Department of Pathology 4 Ben May Department for Cancer Research, University of Chicago, IL Loss of a whole chromosome 5 or a deletion of the long arm, del(5q), is a recurring abnormality in myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML). To identify a leukemia-related gene on chromosome 5, we previously delineated a 970-kb segment of 5q31 that is deleted in all patients examined, and prepared a transcript map of this region. EGR1 is a candidate tumor suppressor gene within the commonly deleted segment of 5q, and encodes a zinc finger transcription factor. To test the hypothesis that loss of function of Egr1 is an initiating event in the pathogenesis of AML/MDS, Egr1-deficient mice were treated with a potent DNA alkylating agent, N-ethyl-nitrosourea (ENU), to induce secondary cooperating mutations. Egr1+/– and Egr1–/– mice treated with ENU developed immature T-cell lymphomas (CD4+, CD8+) or a myeloproliferative disorder (MPD) at increased rates and with shorter latencies than that of wild-type littermates. The MPD was characterized by an elevated white blood cell count, anemia, and thrombocytopenia with ineffective erythropoiesis. Biallelic mutations of Egr1 were not observed in MPDs in Egr1+/– mice. Our data suggest that haploinsufficiency for Egr1 plays a role in murine leukemogenesis, and in the development of AML/MDS characterized by abnormalities of chromosome 5. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Del(5q): gene dosage matters Matthew J. Walter Blood 2007 110: 473-474. [Full Text] [PDF] This article has been cited by other articles: S. D. Nimer Myelodysplastic syndromes Blood, May 15, 2008; 111(10): 4841 - 4851. [Abstract] [Full Text] [PDF] J. Peng, S. M. Kitchen, R. A. West, R. Sigler, K. M. Eisenmann, and A. S. Alberts Myeloproliferative Defects following Targeting of the Drf1 Gene Encoding the Mammalian Diaphanous Related Formin mDia1 Cancer Res., August 15, 2007; 67(16): 7565 - 7571. [Abstract] [Full Text] [PDF] J. Pedersen-Bjergaard, M. T. Andersen, and M. K. Andersen Genetic Pathways in the Pathogenesis of Therapy-Related Myelodysplasia and Acute Myeloid Leukemia Hematology, January 1, 2007; 2007(1): 392 - 397. [Abstract] [Full Text] [PDF] R. A. Larson Etiology and Management of Therapy-Related Myeloid Leukemia Hematology, January 1, 2007; 2007(1): 453 - 459. [Abstract] [Full Text] [PDF]

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