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

doi:10.1016/j.celrep.2016.05.094

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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 language	English
Pages (from-to)	498-507
Number of pages	10
Journal	Cell reports
Volume	16
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2016.05.094
Publication status	Published - 12 Jul 2016
Externally published	Yes

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Vegi, N. M., Klappacher, J., Oswald, F., Mulaw, M. A., Mandoli, A., Thiel, V. N., Bamezai, S., Feder, K., Martens, J. H. A., Rawat, V. P. S., Mandal, T., Quintanilla-Martinez, L., Spiekermann, K., Hiddemann, W., Döhner, K., Döhner, H., Stunnenberg, H. G., Feuring-Buske, M., & Buske, C. (2016). MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML. Cell reports, 16(2), 498-507. https://doi.org/10.1016/j.celrep.2016.05.094

@article{2b17259afc364b288907b4e1d977df12,

title = "MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2016",

year = "2016",

month = jul,

day = "12",

doi = "10.1016/j.celrep.2016.05.094",

language = "English",

volume = "16",

pages = "498--507",

journal = "Cell reports",

issn = "2211-1247",

publisher = "Elsevier BV",

number = "2",

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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 2016, 'MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML', Cell reports, vol. 16, no. 2, pp. 498-507. https://doi.org/10.1016/j.celrep.2016.05.094

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

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 - https://www.scopus.com/pages/publications/84992520065

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 -

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

Abstract

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