Che‐1 is targeted by c‐Myc to sustain proliferation in pre‐B‐cell acute lymphoblastic leukemia Academic Article uri icon

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abstract

  • Despite progress in treating B-cell precursor acute lymphoblastic leukemia (BCP-ALL), disease recurrence remains the main cause of treatment failure. New strategies to improve therapeutic outcomes are needed, particularly in high-risk relapsed patients. Che-1/AATF (Che-1) is an RNA polymerase II-binding protein involved in proliferation and tumor survival, but its role in hematological malignancies has not been clarified. Here, we show that Che-1 is overexpressed in pediatric BCP-ALL during disease onset and at relapse, and that its depletion inhibits the proliferation of BCP-ALL cells. Furthermore, we report that c-Myc regulates Che-1 expression by direct binding to its promoter and describe a strict correlation between Che-1 expression and c-Myc expression. RNA-seq analyses upon Che-1 or c-Myc depletion reveal a strong overlap of the respective controlled pathways. Genomewide ChIP-seq experiments suggest that Che-1 acts as a downstream effector of c-Myc. These results identify the pivotal role of Che-1 in the control of BCP-ALL proliferation and present the protein as a possible therapeutic target in children with relapsed BCP-ALL.

authors

  • Folgiero, Valentina
  • Sorino, Cristina
  • Pallocca, Matteo
  • De Nicola, Francesca
  • Goeman, Frauke
  • Bertaina, Valentina
  • Strocchio, Luisa
  • Romania, Paolo
  • Pitisci, Angela
  • Iezzi, Simona
  • Catena, Valeria
  • Bruno, Tiziana
  • Strimpakos, Georgios
  • Passananti, Claudio
  • Mattei, Elisabetta
  • Blandino, Giovanni
  • Locatelli, Franco
  • Fanciulli, Maurizio

publication date

  • March 2018

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