title: Novel myelofibrosis treatment strategies: potential partners for combination therapies.
abstract: Of the myeloproliferative neoplasms (MPNs), myelofibrosis (MF) is associated with the greatest symptom burden and poorest prognosis and is characterized by constitutional symptoms, cytopenias, splenomegaly and bone marrow fibrosis. A hallmark of MF is dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway that has led to the development of JAK inhibitors targeting this pathway. Calreticulin gene mutations have recently been identified in JAK2 mutation-negative patients with MF. Identification of JAK inhibitor resistance and broad contributions to MF disease pathogenesis from epigenetic deregulators, pathways that work in concert with JAK/STAT (that is, mammalian target of rapamycin/AKT/phosphoinositide 3-kinase, RAS/RAF/MEK, PIM kinase), fibrosis-promoting factors and the MF megakaryocyte, suggest that numerous options may be partnered with a JAK inhibitor. Therefore, we will discuss logical and potential partners for combination therapies for the treatment of patients with MF.
authors.affiliation: 1] Northwestern University Feinberg School of Medicine, Chicago, IL, USA [2] Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Stein
authors.affiliation: Sylvester Comprehensive Cancer Center, Division of Hematology/Oncology, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: R
authors.initials: R
authors.lastname: Swords
authors.affiliation: Klinik für Innere Medizin II, Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors.forename: F
authors.initials: F
authors.lastname: Giles
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000235:genetics; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis
chemical_list: D004791:Enzyme Inhibitors; C507924:JAK2 protein, human; D053614:Janus Kinase 2