TY - JOUR
T1 - MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML
AU - Vegi, Naidu M.
AU - Klappacher, Josef
AU - Oswald, Franz
AU - Mulaw, Medhanie A.
AU - Mandoli, Amit
AU - Thiel, Verena N.
AU - Bamezai, Shiva
AU - Feder, Kristin
AU - Martens, Joost H.A.
AU - Rawat, Vijay P.S.
AU - Mandal, Tamoghna
AU - Quintanilla-Martinez, Leticia
AU - Spiekermann, Karsten
AU - Hiddemann, Wolfgang
AU - Döhner, Konstanze
AU - Döhner, Hartmut
AU - Stunnenberg, Hendrik G.
AU - Feuring-Buske, Michaela
AU - Buske, Christian
N1 - Publisher Copyright:
© 2016
PY - 2016/7/12
Y1 - 2016/7/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84992520065&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2016.05.094
DO - 10.1016/j.celrep.2016.05.094
M3 - Article
C2 - 27346355
AN - SCOPUS:84992520065
SN - 2211-1247
VL - 16
SP - 498
EP - 507
JO - Cell Reports
JF - Cell Reports
IS - 2
ER -