Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and...

Autores
Zunino, Rodolfo; Li, Qinggang; Rosé, Sergio Daniel; Romero-Benítez, María Margarita Itatí; Lejen, Tatiana; Brandan, Nora Cristina; Trifaró, José-María
Año de publicación
2001
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Rapid proliferation of atypical megakaryoblasts is a characteristic of megakaryoblastic leukemia. Cells from patients with this disorder and cell lines established from this type of leukemia showed the presence of gelsolin but the absence of scinderin expression, 2 filamentous actin-severing proteins present in normal megakaryocytes and platelets. Vector-mediated expression of scinderin in the megakaryoblastic cell line MEG-01 induced a decrease in both F-actin and gelsolin. This was accompanied by increased Rac2 expression and by activation of the PAK/MEKK.SEK/JNK/c-jun, c-fos transduction pathway. The Raf/MEK/ERK pathway was also activated in these cells. Transduction pathway activation was followed by cell differentiation, polyploidization, maturation, and apoptosis with release of platelet-like particles. Particles expressed surface CD41a antigen (glycoprotein IIb/IIIa or fibrinogen receptor), had dense bodies, high-affinity serotonin transport, and circular array of microtubules. Treatment of particles with thrombin induced serotonin release and aggregation that was blocked by CD41a antibodies. PAC-1 antibodies also blocked aggregation. Exposure of cells to PD98059, a blocker of MEK, inhibited antigen CD41a expression, increases in cell volume, and number of protoplasmic extensions. Cell proliferation and cell ability to form tumors in nude mice were also inhibited by the expression of scinderin. MEG-01 cells expressing scinderin had the same fate in vivo as in culture. Thus, when injected into nude mice, they entered apoptosis and released platelet-like particles. The lack of scinderin expression in megakaryoblastic leukemia cells seems to be responsible for their inability to enter into differentiation and maturation pathways characteristic of their normal counterparts. © 2001 by The American Society of Hematology.
Fil: Zunino, Rodolfo. University of Ottawa; Canadá
Fil: Li, Qinggang. University of Ottawa; Canadá
Fil: Rosé, Sergio Daniel. University of Ottawa; Canadá
Fil: Romero-Benítez, María Margarita Itatí. University of Ottawa; Canadá
Fil: Lejen, Tatiana. University of Ottawa; Canadá
Fil: Brandan, Nora Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina. University of Ottawa; Canadá
Fil: Trifaró, José-María. University of Ottawa; Canadá
Materia
Meg-01 Cell Line
Pak/Mekk.Sek/Jnk/C-Jun, C-Fos Pathway
Raf/Mek/Erk Pathway
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:11336/60914
Acceder
id CONICETDig_61631192c43d63587d946dd4836b42f0
oai_identifier_str oai:ri.conicet.gov.ar:11336/60914
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesisZunino, RodolfoLi, QinggangRosé, Sergio DanielRomero-Benítez, María Margarita ItatíLejen, TatianaBrandan, Nora CristinaTrifaró, José-MaríaMeg-01 Cell LinePak/Mekk.Sek/Jnk/C-Jun, C-Fos PathwayRaf/Mek/Erk Pathwayhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Rapid proliferation of atypical megakaryoblasts is a characteristic of megakaryoblastic leukemia. Cells from patients with this disorder and cell lines established from this type of leukemia showed the presence of gelsolin but the absence of scinderin expression, 2 filamentous actin-severing proteins present in normal megakaryocytes and platelets. Vector-mediated expression of scinderin in the megakaryoblastic cell line MEG-01 induced a decrease in both F-actin and gelsolin. This was accompanied by increased Rac2 expression and by activation of the PAK/MEKK.SEK/JNK/c-jun, c-fos transduction pathway. The Raf/MEK/ERK pathway was also activated in these cells. Transduction pathway activation was followed by cell differentiation, polyploidization, maturation, and apoptosis with release of platelet-like particles. Particles expressed surface CD41a antigen (glycoprotein IIb/IIIa or fibrinogen receptor), had dense bodies, high-affinity serotonin transport, and circular array of microtubules. Treatment of particles with thrombin induced serotonin release and aggregation that was blocked by CD41a antibodies. PAC-1 antibodies also blocked aggregation. Exposure of cells to PD98059, a blocker of MEK, inhibited antigen CD41a expression, increases in cell volume, and number of protoplasmic extensions. Cell proliferation and cell ability to form tumors in nude mice were also inhibited by the expression of scinderin. MEG-01 cells expressing scinderin had the same fate in vivo as in culture. Thus, when injected into nude mice, they entered apoptosis and released platelet-like particles. The lack of scinderin expression in megakaryoblastic leukemia cells seems to be responsible for their inability to enter into differentiation and maturation pathways characteristic of their normal counterparts. © 2001 by The American Society of Hematology.Fil: Zunino, Rodolfo. University of Ottawa; CanadáFil: Li, Qinggang. University of Ottawa; CanadáFil: Rosé, Sergio Daniel. University of Ottawa; CanadáFil: Romero-Benítez, María Margarita Itatí. University of Ottawa; CanadáFil: Lejen, Tatiana. University of Ottawa; CanadáFil: Brandan, Nora Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina. University of Ottawa; CanadáFil: Trifaró, José-María. University of Ottawa; CanadáAmerican Society of Hematology2001-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/60914Zunino, Rodolfo; Li, Qinggang; Rosé, Sergio Daniel; Romero-Benítez, María Margarita Itatí; Lejen, Tatiana; et al.; Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis; American Society of Hematology; Blood; 98; 7; 10-2001; 2210-22190006-49711528-0020CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1182/blood.V98.7.2210info:eu-repo/semantics/altIdentifier/url/http://www.bloodjournal.org/content/98/7/2210?sso-checked=trueinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:58:20Zoai:ri.conicet.gov.ar:11336/60914instacron: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:34982025-09-29 09:58:21.044CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis
title Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis
spellingShingle Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis
Zunino, Rodolfo
Meg-01 Cell Line
Pak/Mekk.Sek/Jnk/C-Jun, C-Fos Pathway
Raf/Mek/Erk Pathway
title_short Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis
title_full Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis
title_fullStr Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis
title_full_unstemmed Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis
title_sort Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis
dc.creator.none.fl_str_mv Zunino, Rodolfo
Li, Qinggang
Rosé, Sergio Daniel
Romero-Benítez, María Margarita Itatí
Lejen, Tatiana
Brandan, Nora Cristina
Trifaró, José-María
author Zunino, Rodolfo
author_facet Zunino, Rodolfo
Li, Qinggang
Rosé, Sergio Daniel
Romero-Benítez, María Margarita Itatí
Lejen, Tatiana
Brandan, Nora Cristina
Trifaró, José-María
author_role author
author2 Li, Qinggang
Rosé, Sergio Daniel
Romero-Benítez, María Margarita Itatí
Lejen, Tatiana
Brandan, Nora Cristina
Trifaró, José-María
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Meg-01 Cell Line
Pak/Mekk.Sek/Jnk/C-Jun, C-Fos Pathway
Raf/Mek/Erk Pathway
topic Meg-01 Cell Line
Pak/Mekk.Sek/Jnk/C-Jun, C-Fos Pathway
Raf/Mek/Erk Pathway
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Rapid proliferation of atypical megakaryoblasts is a characteristic of megakaryoblastic leukemia. Cells from patients with this disorder and cell lines established from this type of leukemia showed the presence of gelsolin but the absence of scinderin expression, 2 filamentous actin-severing proteins present in normal megakaryocytes and platelets. Vector-mediated expression of scinderin in the megakaryoblastic cell line MEG-01 induced a decrease in both F-actin and gelsolin. This was accompanied by increased Rac2 expression and by activation of the PAK/MEKK.SEK/JNK/c-jun, c-fos transduction pathway. The Raf/MEK/ERK pathway was also activated in these cells. Transduction pathway activation was followed by cell differentiation, polyploidization, maturation, and apoptosis with release of platelet-like particles. Particles expressed surface CD41a antigen (glycoprotein IIb/IIIa or fibrinogen receptor), had dense bodies, high-affinity serotonin transport, and circular array of microtubules. Treatment of particles with thrombin induced serotonin release and aggregation that was blocked by CD41a antibodies. PAC-1 antibodies also blocked aggregation. Exposure of cells to PD98059, a blocker of MEK, inhibited antigen CD41a expression, increases in cell volume, and number of protoplasmic extensions. Cell proliferation and cell ability to form tumors in nude mice were also inhibited by the expression of scinderin. MEG-01 cells expressing scinderin had the same fate in vivo as in culture. Thus, when injected into nude mice, they entered apoptosis and released platelet-like particles. The lack of scinderin expression in megakaryoblastic leukemia cells seems to be responsible for their inability to enter into differentiation and maturation pathways characteristic of their normal counterparts. © 2001 by The American Society of Hematology.
Fil: Zunino, Rodolfo. University of Ottawa; Canadá
Fil: Li, Qinggang. University of Ottawa; Canadá
Fil: Rosé, Sergio Daniel. University of Ottawa; Canadá
Fil: Romero-Benítez, María Margarita Itatí. University of Ottawa; Canadá
Fil: Lejen, Tatiana. University of Ottawa; Canadá
Fil: Brandan, Nora Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina. University of Ottawa; Canadá
Fil: Trifaró, José-María. University of Ottawa; Canadá
description Rapid proliferation of atypical megakaryoblasts is a characteristic of megakaryoblastic leukemia. Cells from patients with this disorder and cell lines established from this type of leukemia showed the presence of gelsolin but the absence of scinderin expression, 2 filamentous actin-severing proteins present in normal megakaryocytes and platelets. Vector-mediated expression of scinderin in the megakaryoblastic cell line MEG-01 induced a decrease in both F-actin and gelsolin. This was accompanied by increased Rac2 expression and by activation of the PAK/MEKK.SEK/JNK/c-jun, c-fos transduction pathway. The Raf/MEK/ERK pathway was also activated in these cells. Transduction pathway activation was followed by cell differentiation, polyploidization, maturation, and apoptosis with release of platelet-like particles. Particles expressed surface CD41a antigen (glycoprotein IIb/IIIa or fibrinogen receptor), had dense bodies, high-affinity serotonin transport, and circular array of microtubules. Treatment of particles with thrombin induced serotonin release and aggregation that was blocked by CD41a antibodies. PAC-1 antibodies also blocked aggregation. Exposure of cells to PD98059, a blocker of MEK, inhibited antigen CD41a expression, increases in cell volume, and number of protoplasmic extensions. Cell proliferation and cell ability to form tumors in nude mice were also inhibited by the expression of scinderin. MEG-01 cells expressing scinderin had the same fate in vivo as in culture. Thus, when injected into nude mice, they entered apoptosis and released platelet-like particles. The lack of scinderin expression in megakaryoblastic leukemia cells seems to be responsible for their inability to enter into differentiation and maturation pathways characteristic of their normal counterparts. © 2001 by The American Society of Hematology.
publishDate 2001
dc.date.none.fl_str_mv 2001-10
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/11336/60914
Zunino, Rodolfo; Li, Qinggang; Rosé, Sergio Daniel; Romero-Benítez, María Margarita Itatí; Lejen, Tatiana; et al.; Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis; American Society of Hematology; Blood; 98; 7; 10-2001; 2210-2219
0006-4971
1528-0020
CONICET Digital
CONICET
url http://hdl.handle.net/11336/60914
identifier_str_mv Zunino, Rodolfo; Li, Qinggang; Rosé, Sergio Daniel; Romero-Benítez, María Margarita Itatí; Lejen, Tatiana; et al.; Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis; American Society of Hematology; Blood; 98; 7; 10-2001; 2210-2219
0006-4971
1528-0020
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1182/blood.V98.7.2210
info:eu-repo/semantics/altIdentifier/url/http://www.bloodjournal.org/content/98/7/2210?sso-checked=true
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
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score 13.070432

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