title: HSP90 and HSP70: Implication in Inflammation Processes and Therapeutic Approaches for Myeloproliferative Neoplasms.
abstract: Myeloproliferative neoplasms (MPN) are clonal stem cell disorders that lead to the excessive production of one or more blood cell lineages. It has been reported that, in most MPN, inflammatory cytokines are frequently increased, indicating that inflammation plays a crucial role in these disorders. Heat shock proteins (HSP) are induced in response to many stressful conditions from heat shock to hypoxia and inflammation. Besides their chaperone and cytoprotective functions, HSPs are key players during inflammation, hence the term "chaperokine." Through their chaperone activity, HSP90, a stabilizer of many oncogenes (e.g., JAK2), and HSP70, a powerful antiapoptotic chaperone, tightly regulate Nuclear Factor-kappa B signalling, a critical pathway in mediating inflammatory responses. In light of this potential, several HSP90 inhibitors have been generated as anticancer agents able to degrade oncogenes. As it turns out, however, these drugs are also potent inhibitors of the inflammatory response in various diseases. Given the chaperone potential of HSP70 and the fact that HSP90 inhibitors induce HSP70, interest in HSP70 inhibitors is also increasing. Here, we focus on the implication of HSP90 and HSP70 in inflammatory responses and on the emergence of new therapeutic approaches in MPN based on HSP inhibitors.
authors.affiliation: INSERM, UMR 866, Equipe Labellisée Ligue contre le Cancer and Association pour la Recherche contre le Cancer, La Ligue Nationale contre le Cancer, Laboratoire d'Excellence LipSTIC, 21000 Dijon, France ; Faculty of Medicine and Pharmacy, University of Burgundy, 21000 Dijon, France.
authors.forename: Margaux
authors.initials: M
authors.lastname: Sevin
authors.affiliation: INSERM, UMR 866, Equipe Labellisée Ligue contre le Cancer and Association pour la Recherche contre le Cancer, La Ligue Nationale contre le Cancer, Laboratoire d'Excellence LipSTIC, 21000 Dijon, France ; Faculty of Medicine and Pharmacy, University of Burgundy, 21000 Dijon, France ; Service d'Hématologie Biologique, Pôle Biologie, 21000 Dijon, France.
authors.forename: François
authors.initials: F
authors.lastname: Girodon
authors.affiliation: INSERM, UMR 866, Equipe Labellisée Ligue contre le Cancer and Association pour la Recherche contre le Cancer, La Ligue Nationale contre le Cancer, Laboratoire d'Excellence LipSTIC, 21000 Dijon, France ; Faculty of Medicine and Pharmacy, University of Burgundy, 21000 Dijon, France ; Centre Anticancéreux Georges-François Leclerc, CGFL, 21000 Dijon, France.
authors.forename: Carmen
authors.initials: C
authors.lastname: Garrido
authors.affiliation: INSERM, UMR 866, Equipe Labellisée Ligue contre le Cancer and Association pour la Recherche contre le Cancer, La Ligue Nationale contre le Cancer, Laboratoire d'Excellence LipSTIC, 21000 Dijon, France ; Faculty of Medicine and Pharmacy, University of Burgundy, 21000 Dijon, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: de Thonel
mesh_terms: D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018836:Inflammation Mediators