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.
authors.affiliation: Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany.
authors.forename: Naidu M
authors.initials: NM
authors.lastname: Vegi
authors.affiliation: Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Klappacher
authors.affiliation: Department of Internal Medicine I, Center for Internal Medicine, University Medical Center Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Oswald
authors.affiliation: Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany.
authors.forename: Medhanie A
authors.initials: MA
authors.lastname: Mulaw
authors.affiliation: Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500HB Nijmegen, the Netherlands.
authors.forename: Amit
authors.initials: A
authors.lastname: Mandoli
authors.affiliation: Department of Internal Medicine I, Center for Internal Medicine, University Medical Center Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Verena N
authors.initials: VN
authors.lastname: Thiel
authors.affiliation: Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany.
authors.forename: Shiva
authors.initials: S
authors.lastname: Bamezai
authors.affiliation: Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Feder
authors.affiliation: Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500HB Nijmegen, the Netherlands.
authors.forename: Joost H A
authors.initials: JHA
authors.lastname: Martens
authors.affiliation: Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany.
authors.forename: Vijay P S
authors.initials: VPS
authors.lastname: Rawat
authors.affiliation: Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany.
authors.forename: Tamoghna
authors.initials: T
authors.lastname: Mandal
authors.affiliation: Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, University Hospital Tübingen, Liebermeisterstrasse 8, 72076 Tübingen, Germany.
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), 81377 Munich, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Spiekermann
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), 81377 Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.affiliation: Department of Internal Medicine III, University Hospital Ulm, 89081 Ulm, Germany.
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
authors.affiliation: Department of Internal Medicine III, University Hospital Ulm, 89081 Ulm, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.affiliation: Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500HB Nijmegen, the Netherlands.
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
authors.affiliation: Department of Internal Medicine III, University Hospital Ulm, 89081 Ulm, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Feuring-Buske
authors.affiliation: Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany; Core Facility Genomics, Medical Faculty Ulm, Ulm University, 89081 Ulm, Germany. Electronic address: christian.buske@uni-ulm.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Buske
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D051575:Proto-Oncogene Proteins c-yes / Q000235:genetics / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D018398:Homeodomain Proteins; C000715470:MAS1 protein, human; C491172:MEIS2 protein, human; D015514:Oncogene Proteins, Fusion; D000090063:Proto-Oncogene Mas; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors; D051575:Proto-Oncogene Proteins c-yes; C489834:YES1 protein, human