Epidemiology and clinical relevance of mutations in postpolycythemia vera and postessential thrombocythemia myelofibrosis: A study on 359 patients of the AGIMM group
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- Giada Rotunno
- CRIMM‐Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Department of Experimental and Clinical Medicine, DENOTHE Excellence Center University of Florence Florence Italy
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- Annalisa Pacilli
- CRIMM‐Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Department of Experimental and Clinical Medicine, DENOTHE Excellence Center University of Florence Florence Italy
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- Valentina Artusi
- Center for Genome Research, and Department of Medical and Surgical Sciences University of Modena and Reggio Emilia Modena, Italy
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- Elisa Rumi
- Department of Hematology Oncology Fondazione IRCCS Policlinico San Matteo Pavia Italy
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- Margherita Maffioli
- Ospedale Di Circolo ‐ Fondazione Macchi University of Insubria Varese Italy
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- Federica Delaini
- Hematology and BMT Unit ASST Papa Giovanni XXIII Bergamo Italy
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- Giada Brogi
- CRIMM‐Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Department of Experimental and Clinical Medicine, DENOTHE Excellence Center University of Florence Florence Italy
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- Tiziana Fanelli
- CRIMM‐Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Department of Experimental and Clinical Medicine, DENOTHE Excellence Center University of Florence Florence Italy
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- Alessandro Pancrazzi
- CRIMM‐Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Department of Experimental and Clinical Medicine, DENOTHE Excellence Center University of Florence Florence Italy
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- Daniela Pietra
- Department of Hematology Oncology Fondazione IRCCS Policlinico San Matteo Pavia Italy
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- Isabella Bernardis
- Center for Genome Research, and Department of Medical and Surgical Sciences University of Modena and Reggio Emilia Modena, Italy
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- Clara Belotti
- Hematology and BMT Unit ASST Papa Giovanni XXIII Bergamo Italy
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- Lisa Pieri
- CRIMM‐Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Department of Experimental and Clinical Medicine, DENOTHE Excellence Center University of Florence Florence Italy
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- Emanuela Sant'Antonio
- CRIMM‐Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Department of Experimental and Clinical Medicine, DENOTHE Excellence Center University of Florence Florence Italy
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- Silvia Salmoiraghi
- Hematology and BMT Unit ASST Papa Giovanni XXIII Bergamo Italy
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- Daniela Cilloni
- Department of Clinical and Biological Sciences University of Turin San Luigi Hospital Turin Turin Italy
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- Alessandro Rambaldi
- Hematology and BMT Unit ASST Papa Giovanni XXIII Bergamo Italy
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- Francesco Passamonti
- Ospedale Di Circolo ‐ Fondazione Macchi University of Insubria Varese Italy
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- Tiziano Barbui
- FROM Research Foundation Ospedale Papa Giovanni XXIII Bergamo Italy
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- Rossella Manfredini
- Department of Life Sciences, Centre for Regenerative Medicine University of Modena and Reggio Emilia Modena Italy
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- Mario Cazzola
- Department of Hematology Oncology Fondazione IRCCS Policlinico San Matteo Pavia Italy
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- Enrico Tagliafico
- Center for Genome Research, and Department of Medical and Surgical Sciences University of Modena and Reggio Emilia Modena, Italy
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- Alessandro M. Vannucchi
- CRIMM‐Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Department of Experimental and Clinical Medicine, DENOTHE Excellence Center University of Florence Florence Italy
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- Paola Guglielmelli
- CRIMM‐Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Department of Experimental and Clinical Medicine, DENOTHE Excellence Center University of Florence Florence Italy
説明
<jats:p>Transformation to secondary myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PPV‐MF) and essential thrombocythemia (PET‐MF). Although primary (PMF) and secondary MF are considered similar diseases and managed similarly, there are few studies specifically focused on the latter. The aim of this study was to characterize the mutation landscape, and describe the main clinical correlates and prognostic implications of mutations, in a series of 359 patients with PPV‐MF and PET‐MF. Compared with PV and ET, the <jats:italic>JAK2</jats:italic>V617F and <jats:italic>CALR</jats:italic> mutated allele burden was significantly higher in PPV‐MF and/or PET‐MF, indicating a role for accumulation of mutated alleles in the process of transformation to MF. However, neither the allele burden nor the type of driver mutation influenced overall survival (OS), while absence of any driver mutation (triple negativity) was associated with significant reduction of OS in PET‐MF, similar to PMF. Of the five interrogated subclonal mutations (<jats:italic>ASXL1, EZH2, SRSF2, IDH1,</jats:italic> and <jats:italic>IDH2</jats:italic>), that comprise a prognostically detrimental high molecular risk (HMR) category in PMF, only <jats:italic>SRSF2</jats:italic> mutations were associated with reduced survival in PET‐MF, and no additional mutation profile with prognostic relevance was highlighted. Overall, these data indicate that the molecular landscape of secondary forms of MF is different from PMF, suggesting that unknown mutational events might contribute to the progression from chronic phase disease to myelofibrosis. These findings also support more extended genotyping approaches aimed at identifying novel molecular abnormalities with prognostic relevance for patients with PPV‐MF and PET‐MF. Am. J. Hematol. 91:681–686, 2016. © 2016 Wiley Periodicals, Inc.</jats:p>
収録刊行物
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- American Journal of Hematology
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American Journal of Hematology 91 (7), 681-686, 2016-05-11
Wiley