Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Leukemia, 2017-11, Vol.31 (11), p.2315-2325

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.