MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML

Naidu M. Vegi, Josef Klappacher, Franz Oswald, Medhanie A. Mulaw, Amit Mandoli, Verena N. Thiel, Shiva Bamezai, Kristin Feder, Joost H.A. Martens, Vijay P.S. Rawat, Tamoghna Mandal, Leticia Quintanilla-Martinez, Karsten Spiekermann, Wolfgang Hiddemann, Konstanze Döhner, Hartmut Döhner, Hendrik G. Stunnenberg, Michaela Feuring-Buske, Christian Buske

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)498-507
Number of pages10
JournalCell Reports
Volume16
Issue number2
DOIs
Publication statusPublished - 12 Jul 2016
Externally publishedYes

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