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

作者：Schneider Edith; Staffas Anna; Roehner Linda; Malmberg Erik D; Ashouri Arghavan; Krowiorz Kathrin; Pochert Nicole; Miller Christina; Wei Stella Yuan; Arabanian Laleh; Buske Christian; Doehner Hartmut; Bullinger Lars; Fogelstrand Linda; Heuser Michael; Doehner Konstanze; Xiang Ping; Ruschmann Jens; Petriv Oleh I; Heravi Moussavi Alireza; Hansen Carl L; Hirst Martin; Humphries R Keith; Rouhi Arefeh; Palmqvist Lars; Kuchenbauer Florian

来源：Haematologica-The Hematology Journal, 2018, 103(2): 246-255.

DOI：10.3324/haematol.2017.177485

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.

• 出版日期2018-2