Annals of Hematology

, Volume 97, Issue 3, pp 443–451 | Cite as

Non-driver mutations in patients with JAK2V617F-mutated polycythemia vera or essential thrombocythemia with long-term molecular follow-up

  • Alicia Senín
  • Concepción Fernández-Rodríguez
  • Beatriz Bellosillo
  • Laura Camacho
  • Raquel Longarón
  • Anna Angona
  • Carles Besses
  • Alberto Álvarez-LarránEmail author
Original Article


JAK2V617F monitoring and NGS of non-driver genes was performed in 100 patients with polycythemia vera (PV) or essential thrombocythemia (ET) with long molecular follow-up. Patients who did not progress to myelofibrosis (MF) or acute myeloid leukemia (AML) after more than 10 years (n = 50) showed a low frequency of mutations at first sample (18%) and an incidence rate of 1.7 new mutations × 100 person-years. Mutations were detected at first sample in 83% of PV/ET patients who later progressed to AML (n = 12) with these patients having a rate of 25.6 mutations × 100 person-years. Presence of mutations at diagnosis was the unique risk factor for acquiring a new genetic event (HR 2.7, 95% CI 1.1–6.8, p = 0.03) after correction for age, PV diagnosis, and total duration of hydroxyurea (HU) exposure. Patients with additional mutation at first sample showed a higher probability of developing cytopenia under HU therapy and a higher risk of AML (HR 12.2, 95% CI 2.6–57.1, p = 0.001) with mutations in ASXL1 (p < 0.0001), TP53 (p = 0.01), SRSF2 (p < 0.0001), IDH1/2 (p < 0.0001), and RUNX1 (p < 0.0001) being associated with a higher probability of AML. Myelofibrotic transformation was more frequent in patients with additional mutations, especially in SF3B1 (p = 0.02) and IDH1/2 (p < 0.0001) although a persistently high or a progressive increase of the JAK2V617F allele burden while receiving cytoreduction was the strongest predictor of MF transformation (HR 10.8, 95% CI 2.4–49.1, p = 0.002). In conclusion, NGS may be useful to identify a minority of PV and ET patients with high genetic instability and increased risk of AML transformation.


Polycythemia vera Essential thrombocythemia Mutations Myelofibrosis Acute myeloid leukemia 



This work was supported by grants from the Instituto de Salud Carlos III, PI13/00557, PI13/0636, PI1300393 and PI16/153, PT13/0010/0005 SGR567, and the “Xarxa de Bancs de tumors” sponsored by Pla Director d’Oncologia de Catalunya (XBTC). Alicia Senín was supported by a grant from the SEHH. CB has received research support for Novartis through his institution for developing this project.


AS and CFR collected the data, performed the molecular studies, and wrote the paper. AA collected the data and approved the final version. RL and LC performed the molecular studies and approved the final version. CB and BB designed the study, interpreted the results, and wrote the paper. AAL designed the study, collected the data, performed the statistical analysis, analyzed and interpreted the results, and wrote the paper.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

277_2017_3193_MOESM1_ESM.xlsx (24 kb)
Table S1 (XLSX 24 kb)
277_2017_3193_MOESM2_ESM.docx (24 kb)
ESM 1 (DOCX 23 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Alicia Senín
    • 1
  • Concepción Fernández-Rodríguez
    • 2
  • Beatriz Bellosillo
    • 2
  • Laura Camacho
    • 2
  • Raquel Longarón
    • 2
  • Anna Angona
    • 1
  • Carles Besses
    • 1
  • Alberto Álvarez-Larrán
    • 1
    Email author
  1. 1.Hematology Department, Hospital del Mar-IMIM (Institut Hospital del Mar d’Investigacions Mèdiques)Universidad Autónoma de BarcelonaBarcelonaSpain
  2. 2.Pathology Department-IMIM, Hospital del MarUniversidad Pompeu FabraBarcelonaSpain

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