Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera. [artículo]
Por: Arenas Cortés, Alicia [Instituto de Investigación i+12]
| Ayala Díaz, Rosa María [Hematología y Hemoterapia] | Barrio García, Santiago [Hematología y Hemoterapia] | Gallardo, Miguel [Hematología y Hemoterapia] | Garcia Martin, Rosa Maria [Anatomía Patológica] | Gilsanz Rodríguez, Florinda [Hematología y Hemoterapia] | Jiménez Ubieto, Ana Isabel [Hematología y Hemoterapia] | Martínez López, Joaquín [Hematología y Hemoterapia] | Toldos González, Oscar [Anatomía Patológica].
Colaborador(es): Servicio de Anatomía Patológica | Servicio de Hematología y Hemoterapia | Instituto de Investigación imas12.
Editor: Molecular cancer, 2013Descripción: 12:142.Recursos en línea: Solicitar documento Resumen: JAK-STAT signaling through the JAK2V617F mutation is central to the pathogenesis of myeloproliferative neoplasms (MPN). However, other events could precede the JAK2 mutation. The aim of this study is to analyze the phenotypic divergence between polycytemia vera (PV) and essential thrombocytemia (ET) to find novel therapeutics targets by a proteomic and functional approach to identify alternative routes to JAK2 activation. Through 2D-DIGE and mass spectrometry of granulocyte protein from 20 MPN samples, showed differential expression of HSP70 in PV and ET besides other 60 proteins. Immunohistochemistry of 46 MPN bone marrow samples confirmed HSP70 expression. The median of positive granulocytes was 80% in PV (SD 35%) vs. 23% in ET (SD 34.25%). In an ex vivo model KNK437 was used as an inhibition model assay of HSP70, showed dose-dependent inhibition of cell growth and burst formation unit erythroid (BFU-E) in PV and ET, increased apoptosis in the erythroid lineage, and decreased pJAK2 signaling, as well as a specific siRNA for HSP70. These data suggest a key role for HSP70 in proliferation and survival of the erythroid lineage in PV, and may represent a potential therapeutic target in MPN, especially in PV.
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Formato Vancouver:
Gallardo M, Barrio S, Fernández M, Paradela A, Arenas A, Toldos O et al. Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera. Mol Cancer. 2013 Nov 19;12:142.
PMID: 24252366
Contiene 35 referencias
JAK-STAT signaling through the JAK2V617F mutation is central to the pathogenesis of myeloproliferative neoplasms (MPN). However, other events could precede the JAK2 mutation. The aim of this study is to analyze the phenotypic divergence between polycytemia vera (PV) and essential thrombocytemia (ET) to find novel therapeutics targets by a proteomic and functional approach to identify alternative routes to JAK2 activation. Through 2D-DIGE and mass spectrometry of granulocyte protein from 20 MPN samples, showed differential expression of HSP70 in PV and ET besides other 60 proteins. Immunohistochemistry of 46 MPN bone marrow samples confirmed HSP70 expression. The median of positive granulocytes was 80% in PV (SD 35%) vs. 23% in ET (SD 34.25%). In an ex vivo model KNK437 was used as an inhibition model assay of HSP70, showed dose-dependent inhibition of cell growth and burst formation unit erythroid (BFU-E) in PV and ET, increased apoptosis in the erythroid lineage, and decreased pJAK2 signaling, as well as a specific siRNA for HSP70. These data suggest a key role for HSP70 in proliferation and survival of the erythroid lineage in PV, and may represent a potential therapeutic target in MPN, especially in PV.
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