Consequences of the JAK2V617F allele burden for the prediction of transformation into myelofibrosis from polycythemia vera and essential thrombocythemia

• Published in: International journal of hematology 2015-02, Vol.101 (2), p.148-153
• Main Authors: Shirane, Shuichi, Araki, Marito, Morishita, Soji, Edahiro, Yoko, Sunami, Yoshitaka, Hironaka, Yumi, Noguchi, Masaaki, Koike, Michiaki, Sato, Eriko, Ohsaka, Akimichi, Komatsu, Norio
• Format: Article
• Language: English
• Subjects: Alleles; Bone Marrow - pathology; Disease Progression; Hematology; Humans; Hydroxyurea - therapeutic use; Janus Kinase 2 - genetics; Medicine; Medicine & Public Health; Mutation; Oncology; Original Article; Polycythemia Vera - genetics; Polycythemia Vera - pathology; Primary Myelofibrosis - diagnosis; Primary Myelofibrosis - drug therapy; Primary Myelofibrosis - genetics; Prognosis; Thrombocythemia, Essential - genetics; Thrombocythemia, Essential - pathology; Time Factors
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-014-1721-9

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 JAK2 V617F, 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 JAK2 V617F 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 JAK2 V617F 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 JAK2 V617F allele burden. In conclusion, a high JAK2 V617F allele burden at initial diagnosis or during follow-up is predictive of MF transformation in PV and ET. Therefore, routine measurement of the JAK2 V617F allele burden using an accurate assay system is recommended to predict MF transformation.