title: Breakthroughs in myeloproliferative neoplasms.
abstract: The discovery of the JAK2V617F mutation ushered the field of Philadelphia-negative myeloproliferative neoplasms (MPNs) into the era of targeted therapy. Currently, there are several JAK2 inhibitors in clinical trials for patients with MPNs, particularly for patients  with myelofibrosis (MF). These drugs act by blocking the proliferation of neoplastic cells by disrupting the JAK2-STAT signaling and by abrogating inflammatory cytokine signaling which is dependent on JAK kinases. Therapy with JAK2 inhibitors can improve splenomegaly and debilitating  constitutional symptoms in great majority of MF patients, improving greatly their quality of life. Long-term follow-up will reveal whether these drugs can also prolong survival by better controlling signs and symptoms of the MF. There are other compounds in clinical trials for MPNs, including  the new immunomodulatory drug pomalidomide, and inhibitor of mammalian target of Rapamycin everolimus. In this article, we briefly review the latest therapeutic advances in the field of Philadelphia-negative MPNs.
authors.affiliation: Hematology and Stem Cell Transplantation, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
authors.forename: Fabio P S
authors.initials: FP
authors.lastname: Santos
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000818:Animals; D000068338:Everolimus; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000201:enzymology; D009570:Nitriles; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D007155:Immunologic Factors; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D013792:Thalidomide; C540383:ruxolitinib; D000068338:Everolimus; C467566:pomalidomide; D053614:Janus Kinase 2; D020123:Sirolimus