title: Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel.
abstract: The Janus kinase 2 mutation, JAK2617V>F, is myeloid neoplasm-specific; its presence excludes secondary polycythemia, thrombocytosis, or bone marrow fibrosis from other causes. Furthermore, JAK2617V>F or a JAK2 exon 12 mutation is present in virtually all patients with polycythemia vera (PV), whereas JAK2617V>F also occurs in approximately half of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Therefore, JAK2 mutation screening holds the promise of a decisive diagnostic test in PV while being complementary to histology for the diagnosis of ET and PMF; the combination of molecular testing and histologic review should also facilitate diagnosis of ET associated with borderline thrombocytosis. Accordingly, revision of the current World Health Organization (WHO) diagnostic criteria for PV, ET, and PMF is warranted; JAK2 mutation analysis should be listed as a major criterion for PV diagnosis, and the platelet count threshold for ET diagnosis can be lowered from 600 to 450 x 10(9)/L. The current document was prepared by an international expert panel of pathologists and clinical investigators in myeloproliferative disorders; it was subsequently presented to members of the Clinical Advisory Committee for the revision of the WHO Classification of Myeloid Neoplasms, who endorsed the document and recommended its adoption by the WHO.
authors.affiliation: Mayo Clinic, Rochester, MN 55905, USA. ayalew@mayo.edu
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
authors.forename: Juergen
authors.initials: J
authors.lastname: Thiele
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.forename: Hans Michael
authors.initials: HM
authors.lastname: Kvasnicka
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barosi
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Gunnar
authors.initials: G
authors.lastname: Birgegard
authors.forename: Ruben
authors.initials: R
authors.lastname: Mesa
authors.forename: John T
authors.initials: JT
authors.lastname: Reilly
authors.forename: Heinz
authors.initials: H
authors.lastname: Gisslinger
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: Francisco
authors.initials: F
authors.lastname: Cervantes
authors.forename: Guido
authors.initials: G
authors.lastname: Finazzi
authors.forename: Ronald
authors.initials: R
authors.lastname: Hoffman
authors.forename: D Gary
authors.initials: DG
authors.lastname: Gilliland
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: James W
authors.initials: JW
authors.lastname: Vardiman
mesh_terms: D006801:Humans; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics; D009154:Mutation; D011087:Polycythemia Vera / Q000175:diagnosis / Q000235:genetics; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000235:genetics; D014944:World Health Organization
chemical_list: D048056:Mitogen-Activated Protein Kinase 9