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Haematologica. 2018 Feb;103(2):246-255. doi: 10.3324/haematol.2017.177485. Epub 2017 Dec 7.

Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia.

Author information

1
Department of Internal Medicine III, University Hospital of Ulm, Germany.
2
Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Sweden.
3
Institute of Biomedicine, University of Gothenburg, Sweden.
4
Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
5
Institute of Experimental Cancer Research, Comprehensive Cancer Centre Ulm, Germany.
6
Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
7
Department of Hematology, Homeostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Germany.
8
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
9
Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada.
10
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada.
11
Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC, Canada.
12
Department of Internal Medicine III, University Hospital of Ulm, Germany florian.kuchenbauer@uni-ulm.de.

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.

PMID:
29217774
PMCID:
PMC5792269
DOI:
10.3324/haematol.2017.177485
[Indexed for MEDLINE]
Free PMC Article

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