Che‐1 is targeted by c‐Myc to sustain proliferation in pre‐B‐cell acute lymphoblastic leukemia |
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| Authors: | Valentina Folgiero Matteo Pallocca Francesca De Nicola Frauke Goeman Valentina Bertaina Luisa Strocchio Paolo Romania Angela Pitisci Simona Iezzi Valeria Catena Tiziana Bruno Georgios Strimpakos Claudio Passananti Elisabetta Mattei Giovanni Blandino Maurizio Fanciulli |
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| Affiliation: | 1. Department of Hematology/Oncology, Bambino Gesù Children's Hospital, IRCCS, Rome, ItalyThese authors contributed equally to this work as first authors;2. SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy;3. Oncogenomic and Epigenetic, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy;4. Department of Hematology/Oncology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy;5. CNR‐Institute of Cell Biology and Neurobiology CNR, IRCCS Fondazione Santa Lucia, Rome, Italy;6. CNR‐Institute of Molecular Biology and Pathology, Department of Molecular Medicine, Sapienza University, Rome, Italy;7. SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, Rome, ItalyThese authors contributed equally to this work as senior authors |
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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. |
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| Keywords: | BCP‐ALL Che‐1 c‐Myc leukemogenesis proliferation |
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