Morgana acts as an oncosuppressor in chronic myeloid leukemia

Autores
Di Savino, Augusta; Panuzzo, Cristina; Rocca, Stefania; Familiari, Ubaldo; Piazza, Rocco; Crivellaro, Sabrina; Carrà, Giovanna; Ferretti, Roberta; Fusella, Federica; Giugliano, Emilia; Camporeale, Annalisa; Franco, Irene; Miniscalco, Barbara; Cutrin, Juan Carlos; Turco, Emilia; Silengo, Lorenzo; Hirsch, Emilio; Rege Cambrin, Giovanna; Gambacorti Passerin, Carlo; Pandolfi, Pier Paolo; Papotti, Mauro; Saglio, Giuseppe; Tarone, Guido; Morotti, Alessandro; Brancaccio, Mara
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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
Materia
Morgana
Centrosome
Chronic Myeloid Leukemia
Rock Inhibitors
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/7914
Acceder
id CONICETDig_2f8d38eaa8e02d14d06c4fdaff8e0254
oai_identifier_str oai:ri.conicet.gov.ar:11336/7914
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Morgana acts as an oncosuppressor in chronic myeloid leukemiaDi Savino, AugustaPanuzzo, CristinaRocca, StefaniaFamiliari, UbaldoPiazza, RoccoCrivellaro, SabrinaCarrà, GiovannaFerretti, RobertaFusella, FedericaGiugliano, EmiliaCamporeale, AnnalisaFranco, IreneMiniscalco, BarbaraCutrin, Juan CarlosTurco, EmiliaSilengo, LorenzoHirsch, EmilioRege Cambrin, GiovannaGambacorti Passerin, CarloPandolfi, Pier PaoloPapotti, MauroSaglio, GiuseppeTarone, GuidoMorotti, AlessandroBrancaccio, MaraMorganaCentrosomeChronic Myeloid LeukemiaRock Inhibitorshttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3We 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; ItaliaFil: Panuzzo, Cristina. Universitã â  Di Torino; ItaliaFil: Rocca, Stefania. Universitã â  Di Torino; ItaliaFil: Familiari, Ubaldo. Universitã â  Di Torino; ItaliaFil: Piazza, Rocco. Universita Degli Studi Di Milano; ItaliaFil: Crivellaro, Sabrina. Universitã â  Di Torino; ItaliaFil: Carrà, Giovanna. Universitã â  Di Torino; ItaliaFil: Ferretti, Roberta. Universitã â  Di Torino; ItaliaFil: Fusella, Federica. Universitã â  Di Torino; ItaliaFil: Giugliano, Emilia. Universitã â  Di Torino; ItaliaFil: Camporeale, Annalisa. Universitã â  Di Torino; ItaliaFil: Franco, Irene. Universitã â  Di Torino; ItaliaFil: Miniscalco, Barbara. Harvard Medical School; Estados UnidosFil: 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); ArgentinaFil: Turco, Emilia. Universita di Torino; ItaliaFil: Silengo, Lorenzo. Universita di Torino; ItaliaFil: Hirsch, Emilio. Universita di Torino; ItaliaFil: Rege Cambrin, Giovanna. Universita di Torino; ItaliaFil: Gambacorti Passerin, Carlo. Universita Degli Studi Di Milano; ItaliaFil: Pandolfi, Pier Paolo. Universita di Torino; Italia. Harvard Medical School; Estados UnidosFil: Papotti, Mauro. Universita di Torino; ItaliaFil: Saglio, Giuseppe. Universita di Torino; ItaliaFil: Tarone, Guido. Universita di Torino; ItaliaFil: Morotti, Alessandro. Universita di Torino; ItaliaFil: Brancaccio, Mara. Universita di Torino; ItaliaAmerican Society Of Hematology2015-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/7914Di Savino, Augusta; Panuzzo, Cristina; Rocca, Stefania; Familiari, Ubaldo; Piazza, Rocco; et al.; Morgana acts as an oncosuppressor in chronic myeloid leukemia; American Society Of Hematology; Blood, The Journal Of The American Society Of Hematology - Print; 125; 4-2015; 2245-22530006-4971enginfo:eu-repo/semantics/altIdentifier/url/http://www.bloodjournal.org/content/125/14/2245.long?sso-checked=trueinfo:eu-repo/semantics/altIdentifier/doi/10.1182/blood-2014-05-575001info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:06:51Zoai:ri.conicet.gov.ar:11336/7914instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:06:52.055CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Morgana acts as an oncosuppressor in chronic myeloid leukemia
title Morgana acts as an oncosuppressor in chronic myeloid leukemia
spellingShingle Morgana acts as an oncosuppressor in chronic myeloid leukemia
Di Savino, Augusta
Morgana
Centrosome
Chronic Myeloid Leukemia
Rock Inhibitors
title_short Morgana acts as an oncosuppressor in chronic myeloid leukemia
title_full Morgana acts as an oncosuppressor in chronic myeloid leukemia
title_fullStr Morgana acts as an oncosuppressor in chronic myeloid leukemia
title_full_unstemmed Morgana acts as an oncosuppressor in chronic myeloid leukemia
title_sort Morgana acts as an oncosuppressor in chronic myeloid leukemia
dc.creator.none.fl_str_mv Di Savino, Augusta
Panuzzo, Cristina
Rocca, Stefania
Familiari, Ubaldo
Piazza, Rocco
Crivellaro, Sabrina
Carrà, Giovanna
Ferretti, Roberta
Fusella, Federica
Giugliano, Emilia
Camporeale, Annalisa
Franco, Irene
Miniscalco, Barbara
Cutrin, Juan Carlos
Turco, Emilia
Silengo, Lorenzo
Hirsch, Emilio
Rege Cambrin, Giovanna
Gambacorti Passerin, Carlo
Pandolfi, Pier Paolo
Papotti, Mauro
Saglio, Giuseppe
Tarone, Guido
Morotti, Alessandro
Brancaccio, Mara
author Di Savino, Augusta
author_facet Di Savino, Augusta
Panuzzo, Cristina
Rocca, Stefania
Familiari, Ubaldo
Piazza, Rocco
Crivellaro, Sabrina
Carrà, Giovanna
Ferretti, Roberta
Fusella, Federica
Giugliano, Emilia
Camporeale, Annalisa
Franco, Irene
Miniscalco, Barbara
Cutrin, Juan Carlos
Turco, Emilia
Silengo, Lorenzo
Hirsch, Emilio
Rege Cambrin, Giovanna
Gambacorti Passerin, Carlo
Pandolfi, Pier Paolo
Papotti, Mauro
Saglio, Giuseppe
Tarone, Guido
Morotti, Alessandro
Brancaccio, Mara
author_role author
author2 Panuzzo, Cristina
Rocca, Stefania
Familiari, Ubaldo
Piazza, Rocco
Crivellaro, Sabrina
Carrà, Giovanna
Ferretti, Roberta
Fusella, Federica
Giugliano, Emilia
Camporeale, Annalisa
Franco, Irene
Miniscalco, Barbara
Cutrin, Juan Carlos
Turco, Emilia
Silengo, Lorenzo
Hirsch, Emilio
Rege Cambrin, Giovanna
Gambacorti Passerin, Carlo
Pandolfi, Pier Paolo
Papotti, Mauro
Saglio, Giuseppe
Tarone, Guido
Morotti, Alessandro
Brancaccio, Mara
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Morgana
Centrosome
Chronic Myeloid Leukemia
Rock Inhibitors
topic Morgana
Centrosome
Chronic Myeloid Leukemia
Rock Inhibitors
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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
description 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.
publishDate 2015
dc.date.none.fl_str_mv 2015-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/7914
Di Savino, Augusta; Panuzzo, Cristina; Rocca, Stefania; Familiari, Ubaldo; Piazza, Rocco; et al.; Morgana acts as an oncosuppressor in chronic myeloid leukemia; American Society Of Hematology; Blood, The Journal Of The American Society Of Hematology - Print; 125; 4-2015; 2245-2253
0006-4971
url http://hdl.handle.net/11336/7914
identifier_str_mv Di Savino, Augusta; Panuzzo, Cristina; Rocca, Stefania; Familiari, Ubaldo; Piazza, Rocco; et al.; Morgana acts as an oncosuppressor in chronic myeloid leukemia; American Society Of Hematology; Blood, The Journal Of The American Society Of Hematology - Print; 125; 4-2015; 2245-2253
0006-4971
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.bloodjournal.org/content/125/14/2245.long?sso-checked=true
info:eu-repo/semantics/altIdentifier/doi/10.1182/blood-2014-05-575001
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society Of Hematology
publisher.none.fl_str_mv American Society Of Hematology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269977728516096
score 13.13397

Publicaciones similares