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
Affiliations
Naidu M. Vegi
Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany
Josef Klappacher
Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany
Franz Oswald
Department of Internal Medicine I, Center for Internal Medicine, University Medical Center Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
Medhanie A. Mulaw
Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany
Amit Mandoli
Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500HB Nijmegen, the Netherlands
Verena N. Thiel
Department of Internal Medicine I, Center for Internal Medicine, University Medical Center Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
Shiva Bamezai
Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany
Kristin Feder
Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany
Joost H.A. Martens
Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500HB Nijmegen, the Netherlands
Vijay P.S. Rawat
Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany
Tamoghna Mandal
Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany
Leticia Quintanilla-Martinez
Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, University Hospital Tübingen, Liebermeisterstrasse 8, 72076 Tübingen, Germany
Karsten Spiekermann
Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), 81377 Munich, Germany
Wolfgang Hiddemann
Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), 81377 Munich, Germany
Konstanze Döhner
Department of Internal Medicine III, University Hospital Ulm, 89081 Ulm, Germany
Hartmut Döhner
Department of Internal Medicine III, University Hospital Ulm, 89081 Ulm, Germany
Hendrik G. Stunnenberg
Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500HB Nijmegen, the Netherlands
Michaela Feuring-Buske
Department of Internal Medicine III, University Hospital Ulm, 89081 Ulm, Germany
Christian Buske
Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany
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.
