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Your search keyword '"Eulàlia Genescà"' showing total 2 results
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2 results on '"Eulàlia Genescà"'

1. Deletion 6q drives T-cell leukemia progression by ribosome modulation

Author

Wouter Van Loocke, Hervé Dombret, Samuel Quentin, Claude Gazin, David Avran, Pieter Van Vlierberghe, François Sigaux, André Baruchel, Delphine Briot, Jean-Jacques Diaz, Stéphanie Gachet, Tom Taghon, Emmanuelle Clappier, Gerben Menschaert, Tiama El-Chaar, Jules P.P. Meijerink, Marika Pla, Eulàlia Genescà, Jessica G.C.A.M. Buijs-Gladdines, Isabelle André-Schmutz, Jean Soulier, Marc Delord, Frédéric Catez, Lucie Hernandez, Willem K. Smits, Godelieve Meunier, Gabriel Therizols, Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Université Paris Diderot - Paris 7 (UPD7), Hémopathies Myéloïdes : Cellules Souches, Modèles Pré-Cliniques et Recherche Translationnelle (UMR 1131), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Princess Máxima Center for Pediatric Oncology, Center for Medical Genetics [Ghent], Ghent University Hospital, Cancer Research Institute (CRIG), Universiteit Gent = Ghent University (UGENT), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Department of Clinical Chemistry, Microbiology and Immunology, Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Collège de France - Chaire Oncologie cellulaire et moléculaire, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Universiteit Gent = Ghent University [Belgium] (UGENT), Chaire Oncologie cellulaire et moléculaire, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS), Ghent University [Belgium] (UGENT), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
0301 basic medicine, Leukemia, T-Cell, Transplantation, Heterologous, T-cell leukemia, Haploinsufficiency, Biology, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Heterogeneous-Nuclear Ribonucleoproteins, Mice, 03 medical and health sciences, RNA interference, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, Gene silencing, Small nucleolar RNA, Gene, ComputingMilieux_MISCELLANEOUS, Gene Expression Profiling, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell biology, Gene expression profiling, 030104 developmental biology, Oncology, Tumor progression, Disease Progression, Chromosomes, Human, Pair 6, RNA Interference, RNA, Long Noncoding, Chromosome Deletion, Ribosomes, TAL1
Abstract

Deletion of chromosome 6q is a well-recognized abnormality found in poor-prognosis T-cell acute lymphoblastic leukemia (T-ALL). Using integrated genomic approaches, we identified two candidate haploinsufficient genes contiguous at 6q14, SYNCRIP (encoding hnRNP-Q) and SNHG5 (that hosts snoRNAs), both involved in regulating RNA maturation and translation. Combined silencing of both genes, but not of either gene alone, accelerated leukemogeneis in a Tal1/Lmo1/Notch1-driven mouse model, demonstrating the tumor-suppressive nature of the two-gene region. Proteomic and translational profiling of cells in which we engineered a short 6q deletion by CRISPR/Cas9 genome editing indicated decreased ribosome and mitochondrial activities, suggesting that the resulting metabolic changes may regulate tumor progression. Indeed, xenograft experiments showed an increased leukemia-initiating cell activity of primary human leukemic cells upon coextinction of SYNCRIP and SNHG5. Our findings not only elucidate the nature of 6q deletion but also highlight the role of ribosomes and mitochondria in T-ALL tumor progression. Significance: The oncogenic role of 6q deletion in T-ALL has remained elusive since this chromosomal abnormality was first identified more than 40 years ago. We combined genomic analysis and functional models to show that the codeletion of two contiguous genes at 6q14 enhances malignancy through deregulation of a ribosome–mitochondria axis, suggesting the potential for therapeutic intervention. This article is highlighted in the In This Issue feature, p. 1494

Published
2018
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2. Preclinical Development of a Bispecific Antibody that Safely and Effectively Targets CD19 and CD47 for the Treatment of B-Cell Lymphoma and Leukemia

Author

Walter Ferlin, Vanessa Buatois, Krzysztof Masternak, Leticia Barba, Françoise Richard, Aditi Dey, Michael P. Rettig, Zoë Johnson, Bruno Daubeuf, Julie Ritchey, Xavier Chauchet, Anne Papaioannou, Eric Hatterer, Robert K. Clarke Hinojosa, Thomas Matthes, Marie Kosco-Vilbois, Thierry Fest, Matilde D'Asaro, Eulàlia Genescà Ferrer, Laura Cons, Limin Shang, Simon LeGallou, Karin Tarte, Katharine Bailey, Nicolas Fischer, Jose Maria Ribera, Adele K. Fielding, Susana Salgado-Pires, Lucile Broyer, Linda Eissenberg, John F. DiPersio, Novimmune SA, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University College of London [London] (UCL), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), R50CA211466, National Cancer Institute, D'Asaro, Matilde, Matthes, Thomas, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Washington University in St Louis

Subjects
Cancer Research, Lymphoma, B-Cell, Antigens, CD19, CD47 Antigen, [SDV.CAN]Life Sciences [q-bio]/Cancer, CD19, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Antigen, Antibodies, Bispecific, medicine, Animals, Humans, ddc:616, Innate immune system, Leukemia, biology, business.industry, CD47, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Xenograft Model Antitumor Assays, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Cancer cell, biology.protein, Cancer research, Rituximab, Antibody, business, 030215 immunology, medicine.drug
Abstract

CD47, an ubiquitously expressed innate immune checkpoint receptor that serves as a universal “don't eat me” signal of phagocytosis, is often upregulated by hematologic and solid cancers to evade immune surveillance. Development of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hemotoxicity including anemia. To overcome such liabilities, we have developed a fully human bispecific antibody, NI-1701, designed to coengage CD47 and CD19 selectively on B cells. NI-1701 demonstrates favorable elimination kinetics with no deleterious effects seen on hematologic parameters following single or multiple administrations to nonhuman primates. Potent in vitro and in vivo activity is induced by NI-1701 to kill cancer cells across a plethora of B-cell malignancies and control tumor growth in xenograft mouse models. The mechanism affording maximal tumor growth inhibition by NI-1701 is dependent on the coengagement of CD47/CD19 on B cells inducing potent antibody-dependent cellular phagocytosis of the targeted cells. NI-1701–induced control of tumor growth in immunodeficient NOD/SCID mice was more effective than that achieved with the anti-CD20 targeted antibody, rituximab. Interestingly, a synergistic effect was seen when tumor-implanted mice were coadministered NI-1701 and rituximab leading to significantly improved tumor growth inhibition and regression in some animals. We describe herein, a novel bispecific antibody approach aimed at sensitizing B cells to become more readily phagocytosed and eliminated thus offering an alternative or adjunct therapeutic option to patients with B-cell malignancies refractory/resistant to anti-CD20–targeted therapy. Mol Cancer Ther; 17(8); 1739–51. ©2018 AACR.

Published
2018
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