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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

57 Citaten (Scopus)


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.

Originele taal-2Engels
Pagina's (van-tot)2315-2325
Aantal pagina's11
Nummer van het tijdschrift11
StatusGepubliceerd - 1 nov. 2017
Extern gepubliceerdJa


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