title: The revised WHO diagnostic criteria for Ph-negative myeloproliferative diseases are not appropriate for the diagnostic screening of childhood polycythemia vera and essential thrombocythemia.
abstract: In the proposed revised World Health Organization (WHO) criteria for the diagnosis of BCR-ABL(-) myeloproliferative diseases (MPDs), exclusion criteria have been replaced by the presence of JAK2 mutations. We applied these criteria to 45 children with MPDs: 13 with polycythemia vera (PV) and 32 with essential thrombocythemia (ET). Among these 45 patients, 12 with ET and 5 with PV had a familial history of MPD, and had been investigated for hereditary mutations of the erythropoietin receptor, thrombopoietin, or MPL genes. We found that the JAK2(V617F) mutation in children occurs less frequently than in adults, and that exon 12 JAK2 mutations are absent. On the basis of the revised WHO criteria, a significant proportion of childhood PVs were misdiagnosed. Furthermore, all familial ET, including patients carrying the hereditary MPL(Ser505Asn) activating mutation, were erroneously diagnosed as MPDs. Our observations suggest that childhood MPDs require a set of specific diagnostic criteria.
authors.affiliation: Department of Hematology, Catholic University, Largo Gemelli 8, 00168 Rome, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Teofili
authors.forename: Fiorina
authors.initials: F
authors.lastname: Giona
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.forename: Tonia
authors.initials: T
authors.lastname: Cenci
authors.forename: Francesco
authors.initials: F
authors.lastname: Guidi
authors.forename: Lorenza
authors.initials: L
authors.lastname: Torti
authors.forename: Giovanna
authors.initials: G
authors.lastname: Palumbo
authors.forename: Angela
authors.initials: A
authors.lastname: Amendola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Leone
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Larocca
mesh_terms: D002648:Child; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000175:diagnosis* / Q000235:genetics; D010677:Philadelphia Chromosome; D011087:Polycythemia Vera / Q000175:diagnosis* / Q000235:genetics; D017467:Receptors, Erythropoietin / Q000235:genetics; D053628:Receptors, Thrombopoietin / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000175:diagnosis* / Q000235:genetics; D013926:Thrombopoietin / Q000235:genetics; D014944:World Health Organization
chemical_list: D017467:Receptors, Erythropoietin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin; C507924:JAK2 protein, human; D053614:Janus Kinase 2