title: Consequences of the JAK2V617F allele burden for the prediction of transformation into myelofibrosis from polycythemia vera and essential thrombocythemia.
abstract: Patients diagnosed with polycythemia vera (PV) or essential thrombocythemia (ET) sometimes suffer transformation of the disease into myelofibrosis (MF), which is associated with a poorer prognosis. This study investigated the prognostic value of the allele burden of JAK2V617F, a somatic driver mutation in these diseases, by comparing the allele burden between formalin-fixed paraffin-embedded bone marrow collected at initial diagnosis and peripheral blood from follow-up visits. Although the annual changes in the JAK2V617F allele burden were comparable between MF-transformed (n = 11) and untransformed (n = 23) patients, the burden was significantly increased in MF-transformed patients exhibiting a longer disease duration than untransformed patients. Furthermore, MF transformation was only observed in patients whose JAK2V617F allele burden exceeded the mean values for each disease (PV, 71.7 %; ET, 35.5 %) at initial diagnosis or during follow-up. Finally, we showed that hydroxycarbamide treatment exerted neither a preventive effect on MF transformation nor a suppressive effect on the increased JAK2V617F allele burden. In conclusion, a high JAK2V617F allele burden at initial diagnosis or during follow-up is predictive of MF transformation in PV and ET. Therefore, routine measurement of the JAK2V617F allele burden using an accurate assay system is recommended to predict MF transformation.
authors.affiliation: Department of Hematology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Shirane
authors.forename: Marito
authors.initials: M
authors.lastname: Araki
authors.forename: Soji
authors.initials: S
authors.lastname: Morishita
authors.forename: Yoko
authors.initials: Y
authors.lastname: Edahiro
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sunami
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hironaka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Noguchi
authors.forename: Michiaki
authors.initials: M
authors.lastname: Koike
authors.forename: Eriko
authors.initials: E
authors.lastname: Sato
authors.forename: Akimichi
authors.initials: A
authors.lastname: Ohsaka
authors.forename: Norio
authors.initials: N
authors.lastname: Komatsu
mesh_terms: D000483:Alleles; D001853:Bone Marrow / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation; D011087:Polycythemia Vera / Q000235:genetics* / Q000473:pathology; D055728:Primary Myelofibrosis / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D011379:Prognosis; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000473:pathology; D013997:Time Factors
chemical_list: D053614:Janus Kinase 2; D006918:Hydroxyurea