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Molecular Cancer
Published in: Molecular Cancer 1/2013

Open Access 01-12-2013 | Research

Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera

Authors: Miguel Gallardo, Santiago Barrio, Marisol Fernandez, Alberto Paradela, Alicia Arenas, Oscar Toldos, Rosa Ayala, Enriqueta Albizua, Ana Jimenez, Santiago Redondo, Rosa Maria Garcia-Martin, Florinda Gilsanz, Juan Pablo Albar, Joaquin Martinez-Lopez

Published in: Molecular Cancer | Issue 1/2013

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Abstract

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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Metadata
Title
Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera
Authors
Miguel Gallardo
Santiago Barrio
Marisol Fernandez
Alberto Paradela
Alicia Arenas
Oscar Toldos
Rosa Ayala
Enriqueta Albizua
Ana Jimenez
Santiago Redondo
Rosa Maria Garcia-Martin
Florinda Gilsanz
Juan Pablo Albar
Joaquin Martinez-Lopez
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2013
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-12-142

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