Haematologica (Feb 2018)
Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia
- Edith Schneider,
- Anna Staffas,
- Linda Röhner,
- Erik D. Malmberg,
- Arghavan Ashouri,
- Kathrin Krowiorz,
- Nicole Pochert,
- Christina Miller,
- Stella Yuan Wei,
- Laleh Arabanian,
- Christian Buske,
- Hartmut Döhner,
- Lars Bullinger,
- Linda Fogelstrand,
- Michael Heuser,
- Konstanze Döhner,
- Ping Xiang,
- Jens Ruschmann,
- Oleh I. Petriv,
- Alireza Heravi-Moussavi,
- Carl L. Hansen,
- Martin Hirst,
- R. Keith Humphries,
- Arefeh Rouhi,
- Lars Palmqvist,
- Florian Kuchenbauer
Affiliations
- Edith Schneider
- Department of Internal Medicine III, University Hospital of Ulm, Germany
- Anna Staffas
- Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Sweden
- Linda Röhner
- Department of Internal Medicine III, University Hospital of Ulm, Germany
- Erik D. Malmberg
- Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Sweden
- Arghavan Ashouri
- Institute of Biomedicine, University of Gothenburg, Sweden
- Kathrin Krowiorz
- Department of Internal Medicine III, University Hospital of Ulm, Germany
- Nicole Pochert
- Department of Internal Medicine III, University Hospital of Ulm, Germany
- Christina Miller
- Department of Internal Medicine III, University Hospital of Ulm, Germany
- Stella Yuan Wei
- Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Sweden;Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
- Laleh Arabanian
- Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Sweden
- Christian Buske
- Institute of Experimental Cancer Research, Comprehensive Cancer Centre Ulm, Germany
- Hartmut Döhner
- Department of Internal Medicine III, University Hospital of Ulm, Germany
- Lars Bullinger
- Department of Internal Medicine III, University Hospital of Ulm, Germany
- Linda Fogelstrand
- Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Sweden;Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
- Michael Heuser
- Department of Hematology, Homeostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Germany
- Konstanze Döhner
- Department of Internal Medicine III, University Hospital of Ulm, Germany
- Ping Xiang
- Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada
- Jens Ruschmann
- Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada
- Oleh I. Petriv
- Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada
- Alireza Heravi-Moussavi
- Canada’s Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada
- Carl L. Hansen
- Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC, Canada
- Martin Hirst
- Canada’s Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada;Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC, Canada
- R. Keith Humphries
- Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada
- Arefeh Rouhi
- Department of Internal Medicine III, University Hospital of Ulm, Germany
- Lars Palmqvist
- Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Sweden;Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
- Florian Kuchenbauer
- Department of Internal Medicine III, University Hospital of Ulm, Germany;Institute of Experimental Cancer Research, Comprehensive Cancer Centre Ulm, Germany
- DOI
- https://doi.org/10.3324/haematol.2017.177485
- Journal volume & issue
-
Vol. 103,
no. 2
Abstract
Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells in vivo. However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected. Although miR-155 accelerated growth and homing in addition to impairing differentiation, our data underscore the pathophysiological relevance of miR-155 as an accelerator rather than a driver of leukemogenesis. This further highlights the complexity of the oncogenic program of Meis1 to compensate for the loss of a potent oncogene such as miR-155. These findings are highly relevant to current and developing approaches for targeting miR-155 in acute myeloid leukemia.
