Morgana acts as an oncosuppressor in chronic myeloid leukemia
| Autor: | Sabrina Crivellaro, Ubaldo Familiari, Mara Brancaccio, Emilia Turco, Alessandro Morotti, Giovanna Carrà, Emilia Giugliano, Rocco Piazza, Mauro Papotti, Juan Carlos Cutrin, Federica Fusella, Cristina Panuzzo, Emilio Hirsch, Carlo Gambacorti-Passerini, Giuseppe Saglio, Giovanna Rege-Cambrin, Lorenzo Silengo, Guido Tarone, Pier Paolo Pandolfi, Roberta Ferretti, Annalisa Camporeale, Irene Franco, Augusta Di Savino, Stefania Rocca, Barbara Miniscalco |
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| Přispěvatelé: | Di Savino, A, Panuzzo, C, Rocca, S, Familiari, U, Piazza, R, Crivellaro, S, Carrà, G, Ferretti, R, Fusella, F, Giugliano, E, Camporeale, A, DE FRANCO, I, Miniscalco, B, Cutrin, J, Turco, E, Silengo, L, Hirsch, E, Rege Cambrin, G, GAMBACORTI PASSERINI, C, Pandolfi, P, Papotti, M, Saglio, G, Tarone, G, Morotti, A, Brancaccio, M |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Fusion Proteins
bcr-abl Immunoenzyme Technique Apoptosis Medicina Clínica Biochemistry Piperazines Immunoenzyme Techniques Mice Bone Marrow hemic and lymphatic diseases rho-Associated Kinase Tumor Cells Cultured Philadelphia Chromosome Mice Knockout rho-Associated Kinases Hematology Reverse Transcriptase Polymerase Chain Reaction Medicine (all) Myeloid leukemia Flow Cytometry Leukemia ROCK INHIBITORS Benzamides Imatinib Mesylate Atypical chronic myeloid leukemia medicine.drug Human medicine.medical_specialty CIENCIAS MÉDICAS Y DE LA SALUD Blotting Western Immunology Protein Kinase Inhibitor Biology Philadelphia chromosome Real-Time Polymerase Chain Reaction MORGANA Benzamide Internal medicine Leukemia Myelogenous Chronic BCR-ABL Positive medicine Animals Humans CENTROSOME Centrosome duplication Hematología RNA Messenger Protein Kinase Inhibitors neoplasms Piperazine Cell Proliferation CHRONIC MYELOID LEUKEMIA Animal Apoptosi Imatinib Cell Biology medicine.disease Molecular biology Mice Inbred C57BL Pyrimidines Imatinib mesylate Pyrimidine Drug Resistance Neoplasm Carrier Proteins Carrier Protein Molecular Chaperones |
| Popis: | We recently described morgana as an essential protein able to regulate centrosome du- plication and genomic stability, by inhibiting ROCK. Here we show that morgana 1/2 mice spontaneously develop a lethal myeloproliferative disease resembling human atypical chronic myeloid leukemia (aCML), preceded by ROCK hyperactivation, centrosome am- plification, and cytogenetic abnormalities in the bone marrow (BM). Moreover, we found that morgana is underexpressed in the BM of patients affected by atypical CML, a disorder of poorly understood molecular basis, characterized by nonrecurrent cytogenetic abnormalities. Morgana is also underexpressed in the BM of a portion of patients affected by Philadelphia-positive CML (Ph1 CML) caused by the BCR-ABL oncogene, and in this condition, morgana underexpression predicts a worse response to imatinib, the standard treatment for Ph1 CML. Thus, morgana acts as an oncosuppressor with different modalities: (1) Morgana underexpression induces centrosome amplifi- cation and cytogenetic abnormalities, and (2) in Ph1 CML, it synergizes with BCR-ABL signaling, reducing the efficacy of imatinib treatment. Importantly, ROCK inhibitionin the BM of patients underexpressing morgana restored the efficacy of imatinib to induce apoptosis, suggesting that ROCK inhibitors, combined with imatinib treatment, can overcome suboptimal responses in patients in which morgana is underex- pressed. Fil: Di Savino, Augusta. Universitã â Di Torino; Italia Fil: Panuzzo, Cristina. Universitã â Di Torino; Italia Fil: Rocca, Stefania. Universitã â Di Torino; Italia Fil: Familiari, Ubaldo. Universitã â Di Torino; Italia Fil: Piazza, Rocco. Universita Degli Studi Di Milano; Italia Fil: Crivellaro, Sabrina. Universitã â Di Torino; Italia Fil: Carrà, Giovanna. Universitã â Di Torino; Italia Fil: Ferretti, Roberta. Universitã â Di Torino; Italia Fil: Fusella, Federica. Universitã â Di Torino; Italia Fil: Giugliano, Emilia. Universitã â Di Torino; Italia Fil: Camporeale, Annalisa. Universitã â Di Torino; Italia Fil: Franco, Irene. Universitã â Di Torino; Italia Fil: Miniscalco, Barbara. Harvard Medical School; Estados Unidos Fil: Cutrin, Juan Carlos. Universitã â Di Torino; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentina Fil: Turco, Emilia. Universita di Torino; Italia Fil: Silengo, Lorenzo. Universita di Torino; Italia Fil: Hirsch, Emilio. Universita di Torino; Italia Fil: Rege Cambrin, Giovanna. Universita di Torino; Italia Fil: Gambacorti Passerin, Carlo. Universita Degli Studi Di Milano; Italia Fil: Pandolfi, Pier Paolo. Universita di Torino; Italia. Harvard Medical School; Estados Unidos Fil: Papotti, Mauro. Universita di Torino; Italia Fil: Saglio, Giuseppe. Universita di Torino; Italia Fil: Tarone, Guido. Universita di Torino; Italia Fil: Morotti, Alessandro. Universita di Torino; Italia Fil: Brancaccio, Mara. Universita di Torino; Italia |
| Databáze: | OpenAIRE |
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