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  • Title: MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML.
    Author: Vegi NM, Klappacher J, Oswald F, Mulaw MA, Mandoli A, Thiel VN, Bamezai S, Feder K, Martens JHA, Rawat VPS, Mandal T, Quintanilla-Martinez L, Spiekermann K, Hiddemann W, Döhner K, Döhner H, Stunnenberg HG, Feuring-Buske M, Buske C.
    Journal: Cell Rep; 2016 Jul 12; 16(2):498-507. PubMed ID: 27346355.
    Abstract:
    Homeobox genes are known to be key factors in leukemogenesis. Although the TALE family homeodomain factor Meis1 has been linked to malignancy, a role for MEIS2 is less clear. Here, we demonstrate that MEIS2 is expressed at high levels in patients with AML1-ETO-positive acute myeloid leukemia and that growth of AML1-ETO-positive leukemia depends on MEIS2 expression. In mice, MEIS2 collaborates with AML1-ETO to induce acute myeloid leukemia. MEIS2 binds strongly to the Runt domain of AML1-ETO, indicating a direct interaction between these transcription factors. High expression of MEIS2 impairs repressive DNA binding of AML1-ETO, inducing increased expression of genes such as the druggable proto-oncogene YES1. Collectively, these data describe a pivotal role for MEIS2 in AML1-ETO-induced leukemia.
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