期刊
BLOOD
卷 110, 期 2, 页码 719-726出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-01-068809
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- NCI NIH HHS [P01 CA040046, CA84221, R01 CA101774, CA40046, R01 CA101774-06, U01 CA084221] Funding Source: Medline
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 erythropolesis. Biallelic mutations of Egr1 were not observed in MPDs in Egr1(+/-)mice. Our data suggest that haploin-sufficiency 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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