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

نویسندگان

  • 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
چکیده

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.

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عنوان ژورنال:

دوره 103  شماره 

صفحات  -

تاریخ انتشار 2018