miR-181a modulates acute myeloid leukemia susceptibility to natural killer cells

Arash Nanbakhsh, Géraldine Visentin, Daniel Olive, Bassam Janji, Eugenie Mussard, Philippe Dessen, Guillaume Meurice, Yanyan Zhang, Fawzia Louache, Jean Henri Bourhis, Salem Chouaib*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

Although daunorubicin (DNR) is the most widely used anthracycline to treat acute myeloid leukemia (AML), resistance to this drug remains a critical problem. The aim of this study was to investigate the relationship between AML resistance to daunorubicin and susceptibility to natural killer (NK) cell-mediated cell lysis, and the putative expression of miRs. For this purpose, we used the parental AML cell lines U-937 and KG-1 and their equivalent resistant U937(R) and KG-1(R) cell lines. We demonstrate for the first time that the acquisition of resistance to DNR by the parental cell lines resulted in the acquisition of cross-resistance to NK cell-mediated cytotoxicity. miR microarray analysis revealed that this cross-resistance was associated with miR-181a downregulation and the subsequent regulation of MAP3K10 and MAP2K1 tyrosine kinases and the BCL-2 (BCL-2 and MCL-1) family. Overexpression of miR-181a in AML blasts resulted in the attenuation of their resistance to DNR and to NK-cell-mediated killing. These data point to a determinant role of miR-181a in the sensitization of leukemic resistant cells to DNR and NK cells and suggest that miR-181a may provide a promising option for the treatment of immuno- and chemo-resistant blasts.

Original languageEnglish
JournalOncoImmunology
Volume4
Issue number12
DOIs
Publication statusPublished - 2 Dec 2015

Keywords

  • AML
  • NK lysis
  • miR-181a

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