Heat Shock Protein 90 is overexpressed in high-risk myelodysplastic syndromes and associated with higher expression and activation of Focal Adhesion Kinase

摘要: // Pascale Flandrin-Gresta 1,2 , Francoise Solly Carmen Mariana Aanei 1 Jerome Cornillon 3 Emmanuelle Tavernier 2,3 Nathalie Nadal Franck Morteux 2 Denis Guyotat Eric Wattel Lydia Campos Laboratoire d’Hematologie, University Hospital of Saint-Etienne, 42055 Saint-Etienne Cedex 2, France. UMR5239 CNRS, Universite Claude Bernard Lyon 1, Faculte deMedecine J Lisfranc 42023 Institut de Cancerologie la Loire, 42271 Saint Priesten Jarez cedex, Correspondence: Flandrin-Gresta, email: Keywords : HSP90, MDS, FAK, 17-AAG Received July 18, 2012, Accepted September 25, Published 28, 2012 Abstract Myelodysplastic syndromes are characterized by a high risk evolution into acute myeloid leukaemia which can involve activation signalling pathways. As the chaperone heat shock protein 90 (HSP90) has key role in signal transduction, we investigated its pathogenesis and myelodysplastic syndromes. Expressions HSP90 proteins clients (phosphorylated-AKT (pAKT), Focal Adhesion Kinase (FAK) phosphorylated-FAK (pFAK)), were assessed bone marrow mononuclear CD34-positive (CD34 + ) cells from 177 patients with myelodysplasia. Effects inhibition also evaluated 39 samples. The levels all studied significantly higher grade disease, than those low syndrome or chronic myelomonocytic leukaemia. High pFAK pAKT associated shorter survival increased progression A down regulation apoptosis was observed CD34 after 12 hours incubation 17-AAG. In conclusion, our data suggest implication FAK AKT excess blasts to Moreover this network could be therapeutic target through inhibition.