Primary acute myeloid leukemia cells with overexpression of EVI-1 are sensitive to all-trans retinoic acid

Blood. 2016 Jan 28;127(4):458-63. doi: 10.1182/blood-2015-07-653840. Epub 2015 Nov 18.


Enhanced expression of ecotropic viral integration site 1 (EVI-1) occurs in ∼10% of acute myeloid leukemia (AML) patients and is associated with a very poor disease outcome. Patients with EVI-1-positive AML have poor initial responses to chemotherapy and high relapse rates, indicating an urgent need for alternative treatment strategies improving clinical outcome for these patients. Because treatment of acute promyelocytic patients with all-trans retinoic acid (ATRA) has improved the survival of these patients substantially, we investigated whether ATRA might also be effective for the subgroup of AML patients with EVI-1 overexpression. Here, we show that a substantial part of the EVI-1-positive AML cases respond to ATRA by induction of differentiation and decreased clonogenic capacity of myeloid blasts. Most importantly, we demonstrate that in vivo treatment of primary EVI-1-positive AML with ATRA leads to a significant reduction in leukemic engraftment. Altogether, our results show that a considerable part of the EVI-1-positive primary AML cases are sensitive to ATRA, suggesting that combining ATRA with the currently used conventional chemotherapy might be a promising treatment strategy decreasing relapse rates and enhancing complete remissions in this poor prognostic subgroup of AML patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Differentiation / drug effects
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics*
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology
  • MDS1 and EVI1 Complex Locus Protein
  • Male
  • Mice, SCID
  • Myeloid Cells / cytology
  • Myeloid Cells / drug effects
  • Myeloid Cells / metabolism
  • Myeloid Cells / pathology
  • Proto-Oncogenes / genetics*
  • Transcription Factors / analysis
  • Transcription Factors / genetics*
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured
  • Up-Regulation


  • Antineoplastic Agents
  • DNA-Binding Proteins
  • MDS1 and EVI1 Complex Locus Protein
  • MECOM protein, human
  • Transcription Factors
  • Tretinoin