MiR-194-5p/BCLAF1 deregulation in AML tumorigenesis

C. Dell'Aversana, C. Giorgio, L. D'Amato, G. Lania, F. Matarese, S. Saeed, A. Di Costanzo, V. Belsito Petrizzi, C. Ingenito, J. H.A. Martens, I. Pallavicini, S. Minucci, A. Carissimo, H. G. Stunnenberg, L. Altucci

Research output: Contribution to journalArticle

Abstract

Deregulation of epigenetic mechanisms, including microRNA, contributes to leukemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal hematopoietic progenitors. In acute myeloid leukemias this balance is perturbed, locking cells into an immature, potentially 'immortal' state. Enhanced expression of miR-194-5p by treatment with the histone deacetylase inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol. miR-194-5p/BCLAF1 balance was found commonly deregulated in 60 primary acute myeloid leukemia patients and was largely restored by ex vivo SAHA treatment. Our findings link treatment responsiveness to re-instatement of miR-194-5p/BCLAF1 balance.

Original languageEnglish
Pages (from-to)2315-2325
Number of pages11
JournalLeukemia
Volume31
Issue number11
DOIs
Publication statusPublished - Nov 1 2017

    Fingerprint

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Dell'Aversana, C., Giorgio, C., D'Amato, L., Lania, G., Matarese, F., Saeed, S., Di Costanzo, A., Belsito Petrizzi, V., Ingenito, C., Martens, J. H. A., Pallavicini, I., Minucci, S., Carissimo, A., Stunnenberg, H. G., & Altucci, L. (2017). MiR-194-5p/BCLAF1 deregulation in AML tumorigenesis. Leukemia, 31(11), 2315-2325. https://doi.org/10.1038/leu.2017.64