학술논문
MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML
Document Type
article
Author
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
Source
Cell Reports, Vol 16, Iss 2, Pp 498-507 (2016)
Subject
Language
English
ISSN
2211-1247
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.