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

John M. Joslin, Anthony A. Fernald, Thelma R. Tennant, Elizabeth M. Davis, Scott C. Kogan, John Anastasi, John D. Crispino, Michelle M. Le Beau*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

187 Scopus citations


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 litter-mates. 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.

Original languageEnglish (US)
Pages (from-to)719-726
Number of pages8
Issue number2
StatePublished - Jul 15 2007

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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