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Haploinsufficiency of EGR1, a candidate gene in the del(5q), leads to the development of myeloid disorders.

Authors: Joslin, JM  Fernald, AA  Tennant, TR  Davis, EM  Kogan, SC  Anastasi, J  Crispino, JD  Le Beau, MM 
Citation: Joslin JM, etal., Blood. 2007 Jul 15;110(2):719-26. Epub 2007 Apr 9.
Pubmed: (View Article at PubMed) PMID:17420284
DOI: Full-text: DOI:10.1182/blood-2007-01-068809

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.

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CRRD Object Information
CRRD ID: 5131859
Created: 2011-05-11
Species: All species
Last Modified: 2011-05-11
Status: ACTIVE



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