JAK2V617F variant allele frequency50% identifies patients with polycythemia vera at high risk for venous thrombosis
| Autor: | Paola Guglielmelli, Giuseppe G. Loscocco, Carmela Mannarelli, Elena Rossi, Francesco Mannelli, Francesco Ramundo, Giacomo Coltro, Silvia Betti, Chiara Maccari, Sara Ceglie, Patrizia Chiusolo, Chiara Paoli, Tiziano Barbui, Ayalew Tefferi, Valerio De Stefano, Alessandro M. Vannucchi |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Aged 80 and over Male Venous Thrombosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens Hematology Janus Kinase 2 Middle Aged Article Young Adult Myeloproliferative disease Oncology Gene Frequency Risk Factors Humans Point Mutation Female Polycythemia Vera Cancer genetics RC254-282 Aged Retrospective Studies |
| Zdroj: | Blood Cancer Journal Blood Cancer Journal, Vol 11, Iss 12, Pp 1-9 (2021) |
| ISSN: | 2044-5385 |
| Popis: | Arterial (AT) and venous (VT) thrombotic events are the most common complications in patients with polycythemia vera (PV) and are the leading causes of morbidity and mortality. In this regard, the impact of JAK2V617F variant allele frequency (VAF) is still debated. The purpose of the current study was to analyze the impact of JAK2V617F VAF in the context of other established risk factors for thrombosis in a total of 865 2016 WHO-defined PV patients utilizing two independent cohorts: University of Florence (n = 576) as a training cohort and Policlinico Gemelli, Catholic University, Rome (n = 289) as a validation cohort. In the training cohort VT free-survival was significantly shorter in the presence of a JAK2V617F VAF > 50% (HR 4; p p = 0.8). Multivariable analysis identified JAK2V617F VAF > 50% (HR 3.8, p = 0.001) and previous VT (HR 2.2; p = 0.04) as independent risk factors for future VT whereas diabetes (HR 2.4; p = 0.02), hyperlipidemia (HR 2.3; p = 0.01) and previous AT (HR 2; p = 0.04) were independent risk factors for future AT. Similarly, JAK2V617F VAF > 50% (HR 2.4; p = 0.01) and previous VT (HR 2.8; p = 0.005) were confirmed as independent predictors of future VT in the validation cohort. Impact of JAK2V617F VAF > 50% on VT was particularly significant in conventional low-risk patients, both in Florence (HR 10.6, p = 0.005) and Rome cohort (HR 4; p = 0.02). In conclusion, we identified JAK2V617F VAF > 50% as an independent strong predictor of VT, supporting that AT and VT are different entities which might require distinct management. |
| Databáze: | OpenAIRE |
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