title: Myeloproliferative neoplasms: from JAK2 mutations discovery to JAK2 inhibitor therapies.
abstract: Most BCR-ABL1-negative myeloproliferative neoplasms (MPN) carry an activating JAK2 mutation. Approximately 96% of patients with polycythemia vera (PV) harbors the V617F mutation in JAK2 exon 14, whereas the minority of JAK2 (V617F)-negative subjects shows several mutations in exon 12. Other mutation events as MPL, TET2, LNK, EZH2 have been described in chronic phase, while NF1, IDH1, IDH2, ASX1, CBL and Ikaros in blast phase of MPN. The specific pathogenic implication of these mutations is under investigation, but they may have a role in refinement of diagnostic criteria and in development of new prognostic models. Several trials with targeted therapy (JAK inhibitors) are ongoing mostly involving patients with PMF, post-PV MF and post-essential thrombocythemia (ET) MF. Treatment with ruxolitinib and TG101348 has shown clinically significant benefits, particularly in improvement of splenomegaly and constitutional symptoms in MF patients. On the other hand, JAK inhibitors have not thus far shown disease-modifying activity therefore any other deduction on these new drugs seems premature.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Ospedale di Circolo e Fondazione Macchi, Varese, Italy. francesco.passamonti@ospedale.varese.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Passamonti
authors.forename: Margherita
authors.initials: M
authors.lastname: Maffioli
authors.forename: Domenica
authors.initials: D
authors.lastname: Caramazza
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019046:Bone Marrow Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D004252:DNA Mutational Analysis; D056726:Genetic Association Studies; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics; D009154:Mutation / Q000502:physiology; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C507924:JAK2 protein, human; D053614:Janus Kinase 2