Distinct roles for PARP-1 and PARP-2 in c-Myc-driven B-cell lymphoma in mice.

Autor:	Galindo-Campos MA; Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain., Lutfi N; Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain., Bonnin S; Center for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain., Martínez C; Experimental Pathology Unit, Instituto Murciano de Investigación Biosanitaria-Laboratorio de Investigación Biosanitaria-Arrixaca, Murcia, Spain., Velasco-Hernandez T; Josep Carreras Leukemia Research Institute, Barcelona, Spain.; Instituto de Salud Carlos III (ISCIII), Redes de Investigación Cooperativa Orientadas a Resultados en Salud, Madrid, Spain., García-Hernández V; Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain., Martín-Caballero J; Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain., Ampurdanés C; Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain., Gimeno R; Laboratory of Immunology, Department of Pathology., Colomo L; Department of Pathology, Hospital del Mar, Barcelona, Spain., Roué G; Josep Carreras Leukemia Research Institute, Barcelona, Spain., Guilbaud G; Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom., Dantzer F; Biotechnology and Cell Signaling, Unité Mixte de Recherche (UMR) 7242 Centre National de la Recherche Scientifique, Laboratory of Excellence Medalis, École Supérieure de Biotechnologie de Strasbourg, Strasbourg University, Illkirch, France., Navarro P; Institute of Biomedical Research of Barcelona (IIBB)-CSIC, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.; Hospital del Mar Medical Research Institute, Unidad Asociada IIBB-CSIC, Barcelona, Spain., Murga M; Genomic Instability Group, Spanish National Cancer Research Centre, Madrid, Spain., Fernández-Capetillo O; Genomic Instability Group, Spanish National Cancer Research Centre, Madrid, Spain.; Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Bigas A; Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.; Josep Carreras Leukemia Research Institute, Barcelona, Spain.; ISCIII, Centro de Investigación Biomédica en Red de Oncología, Barcelona, Spain; and., Menéndez P; Josep Carreras Leukemia Research Institute, Barcelona, Spain.; Instituto de Salud Carlos III (ISCIII), Redes de Investigación Cooperativa Orientadas a Resultados en Salud, Madrid, Spain.; ISCIII, Centro de Investigación Biomédica en Red de Oncología, Barcelona, Spain; and.; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain., Sale JE; Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom., Yélamos J; Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.; Laboratory of Immunology, Department of Pathology.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2022 Jan 13; Vol. 139 (2), pp. 228-239.
DOI:	10.1182/blood.2021012805
Abstrakt:	Dysregulation of the c-Myc oncogene occurs in a wide variety of hematologic malignancies, and its overexpression has been linked with aggressive tumor progression. Here, we show that poly (ADP-ribose) polymerase 1 (PARP-1) and PARP-2 exert opposing influences on progression of c-Myc-driven B-cell lymphoma. PARP-1 and PARP-2 catalyze the synthesis and transfer of ADP-ribose units onto amino acid residues of acceptor proteins in response to DNA strand breaks, playing a central role in the response to DNA damage. Accordingly, PARP inhibitors have emerged as promising new cancer therapeutics. However, the inhibitors currently available for clinical use are not able to discriminate between individual PARP proteins. We found that genetic deletion of PARP-2 prevents c-Myc-driven B-cell lymphoma, whereas PARP-1 deficiency accelerates lymphomagenesis in the Eμ-Myc mouse model of aggressive B-cell lymphoma. Loss of PARP-2 aggravates replication stress in preleukemic Eμ-Myc B cells, resulting in accumulation of DNA damage and concomitant cell death that restricts the c-Myc-driven expansion of B cells, thereby providing protection against B-cell lymphoma. In contrast, PARP-1 deficiency induces a proinflammatory response and an increase in regulatory T cells, likely contributing to immune escape of B-cell lymphoma, resulting in an acceleration of lymphomagenesis. These findings pinpoint specific functions for PARP-1 and PARP-2 in c-Myc-driven lymphomagenesis with antagonistic consequences that may help inform the design of new PARP-centered therapeutic strategies, with selective PARP-2 inhibition potentially representing a new therapeutic approach for the treatment of c-Myc-driven tumors. (© 2022 by The American Society of Hematology.)
Databáze:	MEDLINE
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