MicroRNA-155 is upregulated in MLL-rearranged AML but its absence does not affect leukemia development

Exp Hematol. 2016 Dec;44(12):1166-1171. doi: 10.1016/j.exphem.2016.08.012. Epub 2016 Sep 13.

Abstract

MicroRNA-155 (miR-155) is an oncogenic miRNA upregulated in various tumor types and leukemias and has been suggested as a potential drug target. Based on our previous work detecting high miR-155 levels in response to Meis1 overexpression in a murine Hox leukemia model, we show here the relationship among HOXA9, MEIS1, and miR-155 levels in MLL-translocated acute myeloid leukemia (AML) patients. Using mouse bone marrow cells transformed by MLL-fusion genes expressing graduated levels of Meis1, we show a positive correlation between miR-155 and Meis1. However, using a miR-155-knockout mouse model, we show that the absence and the depletion of miR-155 have no effect on leukemia formation or progression. We also show for the first time that miR-155 levels are correlated with MLL translocations, but that miR-155 expression is dispensable for the formation of AML and has no effect on leukemia progression.

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Bone Marrow Transplantation
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gene Expression Regulation, Leukemic*
  • Gene Knockout Techniques
  • Gene Rearrangement*
  • Homeodomain Proteins / genetics
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Mice
  • MicroRNAs / genetics*
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Neoplasm Proteins / genetics
  • Oncogene Proteins, Fusion*

Substances

  • Homeodomain Proteins
  • MEIS1 protein, human
  • MIRN155 microRNA, human
  • Meis1 protein, mouse
  • MicroRNAs
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • homeobox protein HOXA9
  • Myeloid-Lymphoid Leukemia Protein