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

DOI
https://doi.org/10.3324/haematol.2017.177485
Journal volume & issue
Vol. 103, no. 2

Abstract

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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.