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Driver mutations’ effect in secondary myelofibrosis: an international multicenter study based on 781 patients

Leukemia volume 31, pages 970–973 (2017)Cite this article

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Essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) are the classic BCR/ABL1-negative myeloproliferative neoplasms (MPN).1 PV and ET can progress to secondary myelofibrosis (SMF),2, 3 referred to as post-PV (PPV) myelofibrosis (MF) and post-ET (PET) MF.4 The genomic landscape of MPN has changed in the last decade leading to a mandatory testing of all known phenotypic driver mutations of the JAK2, MPL, CALR genes.1 Translational implications of somatic genomics in MPN are well known in patients with PMF,5 while information on SMF is scant.6, 7, 8, 9 A recent study on 165 PET MF showed that JAK2-mutated patients are more frequently symptomatic, had larger spleen size, higher IPSS risk and had more thromboses and that CALR type 1-mutated patients had a lower rate of death.6 The molecular anatomy of SMF is slightly different from that of PMF with mutations in ASXL1, EZH2, SRSF2, IDH1, and IDH2 present in 25% of patients. Differently from PMF,10 these mutations have no implication on SMF outcome prediction, with the exception of SRSF2 mutations, which correlate with reduced survival.6

The need for clinical and molecular information in SMF led to the development of the MYSEC (MYelofibrosis SECondary to PV and ET) project, an international effort generated in 2014 to collect retrospective data on SMF. In the current work, we studied the largest cohort to date of SMF patients, including 781 consecutive patients (397 PET MF, 384 PPV MF) collected from 16 international centers and followed for a median time of 3.0 years (range, 0.6–27.3). Information on the three driver mutations was available in 337 (85%) PET MF and in 352 (92%) PPV MF. All patients have demographic, clinical and hematologic data at SMF diagnosis and were regularly followed for events. No differences in disease presentation (white blood cell count, hemoglobin level, platelet count) have been observed among centers applying pairwise Wilcoxon rank tests. Part of the patients has been included in a prior study.6

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Acknowledgements

This work was supported by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC; Milano, Italy), Special Program Molecular Clinical Oncology 5x1000 to AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM) project #1005. A complete list of AGIMM investigators is available at http://www.progettoagimm.it Supported also by AIRC IG2014-15967 and by Ministero della Salute (project code GR-2011-02352109) to PG. Varese group was also supported by a grant from the Fondazione Matarelli (Milano, Italy), Fondazione Rusconi (Varese, Italy) and AIL Varese ONLUS.

Author contributions

FP, AMV, MC, BM and MM contributed to the conception of the work; FP, TG and BM contributed to the design of the work; FP, BM, PG, MC, MM, AR, MC, RK, JG, JJK, FC, TD, NV, VDS, MR, RS, GB, FA, DC, ER, MMe, DP, RC, TB, LP and AMV contributed to the acquisition, analysis or interpretation of data for the work; FP, BM, TG, PG, MC, MM, AR, MC, RK, JG, JJK, FC, TD, NV, VDS, MR, RS, GB, FA, DC, ER, MMe, DP, RC, TB, LP and AMV contributed to revising the manuscript critically for important intellectual content and approved the final version of the manuscript; TG was responsible for the statistical analysis.

Author information

Author notes

  1. B Mora and T Giorgino: These authors contributed equally to this work.

  2. FROM Research Foundation, ASST Papa Giovanni XXIII, Bergamo, Italy

Authors and Affiliations

  1. Division of Hematology, Department of Clinical and Experimental Medicine, University of Insubria, Ospedale di Circolo, ASST Sette Laghi, Varese, Italy

    F Passamonti, B Mora, M Maffioli, D Caramazza & M Merli

  2. Institute of Neurosciences, National Research Council of Italy, Padova, Italy

    T Giorgino & L Pieri

  3. Department of Experimental and Clinical Medicine, CRIMM-Centro Ricerca e Innovazione delle Malattie Mieloproloiferative, Azienda ospedaliera-Universitaria Careggi, University of Florence, Florence, Italy

    P Guglielmelli & A M Vannucchi

  4. Department of Oncology and Hematology, Università di Pavia, Pavia, Italy

    M Cazzola, A Rambaldi, E Rumi & D Pietra

  5. Department of Hematology and BMT Unit, University of Milan, ASST Papa Giovanni XXIII, Bergamo, Italy

    M Caramella

  6. Department of Oncology and Hematology Ospedale Niguarda Cà Granda, Milano, Italy

    R Komrokji

  7. Malignant Hematology Department, Moffit Cancer Center, Tampa, FL, USA

    J Gotlib

  8. Division of Hematology, Stanford University, Palo Alto, CA, USA

    J J Kiladjian

  9. Hôpital Saint-Louis et Université Paris Diderot, Paris, France

    F Cervantes

  10. Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain

    T Devos

  11. Department of Hematology, University Hospitals Leuven, Leuven, Belgium

    F Palandri

  12. Department of Oncology and Hematology, Policlinico S. Orsola-Malpighi, Bologna, Italy

    V De Stefano

  13. Institute of Hematology, Università Cattolica del Sacro Cuore, Roma, Italy

    M Ruggeri

  14. Department of Oncology and Hematology, Ospedale S. Bortolo, Vicenza, Italy

    R Silver

  15. Weill Cornell Medical College, New York, NY, USA

    G Benevolo

  16. Centro Oncologico Ematologico Subalpino (COES), Torino, Italy

    F Albano

  17. Department of Oncology and Hematology Università di Bari, Bari, Italy

    R Casalone

  18. Department of Services, Cytogenetics and Medical Genetics Laboratory, Ospedale di Circolo, ASST Sette Laghi, Varese, Italy

    T Barbui

Authors
  1. F Passamonti
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  2. B Mora
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  19. F Albano
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  20. D Caramazza
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  21. E Rumi
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  26. L Pieri
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Correspondence to F Passamonti.

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Passamonti, F., Mora, B., Giorgino, T. et al. Driver mutations’ effect in secondary myelofibrosis: an international multicenter study based on 781 patients. Leukemia 31, 970–973 (2017). https://doi.org/10.1038/leu.2016.351

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