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Che‐1 is targeted by c‐Myc to sustain proliferation in pre‐B‐cell acute lymphoblastic leukemia
Author(s) -
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 year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744871
Subject(s) - lymphoblastic leukemia , cancer research , cell growth , leukemia , biology , immunology , genetics
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 Ch IP ‐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 .