Abstract
BackgroundThe driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation. Pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers potentially useful for refining prognostic classification of MPNs.MethodsWe evaluated 305 with essential thrombocythemia (ET) and 172 polycythemia vera (PV) patients diagnosed according to the 2016 WHO criteria and with full molecular characterization for driver mutations.ResultsPTX3 levels were significantly increased in carriers of homozygous JAK2V617F mutation compared to all the other genotypes and triple negative ET patients, while hs-CRP levels were independent of the mutational profile. The risk of haematological evolution and death from any cause was about 2- and 1.5-fold increased in individuals with high PTX-3 levels, while the thrombosis rate tended to be lower. High hs-CRP levels were associated with risk of haematological evolution, death and also major thrombosis. After sequential adjustment for potential confounders (age, gender, diagnosis and treatments) and the presence of JAK2V617F homozygous status, high hs-CRP levels remained significant for all outcomes, while JAK2V617F homozygous status as well as treatments were the factors independently accounting for adverse outcomes among patients with high PTX3 levels.ConclusionsThese results provide evidence that JAK2V617F mutation influences MPN-associated inflammation with a strong correlation between allele burden and PTX3 levels. Plasma levels of hs-CRP and PTX3 might be of prognostic value for patients with ET and PV, but their validation in future prospective studies is needed.
Highlights
The driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation
These studies demonstrated that somatic mutations, by determining a more pronounced activation of platelets, leukocytes and endothelial cells [10, 11] and promoting an increased number of leukocytes [12] can sustain a condition of chronic inflammation, which may contribute to the premature atherosclerosis underlying the cardiovascular events and to clonal evolution and second cancer [2, 13,14,15,16,17]
Aspirin was prescribed in the majority of cases and cytoreductive treatments were given in 57% and 64% of essential thrombocythemia (ET) and Polycythemia vera (PV) cases, respectively
Summary
The driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation. These studies demonstrated that somatic mutations, by determining a more pronounced activation of platelets, leukocytes and endothelial cells [10, 11] and promoting an increased number of leukocytes [12] can sustain a condition of chronic inflammation, which may contribute to the premature atherosclerosis underlying the cardiovascular events and to clonal evolution and second cancer [2, 13,14,15,16,17] Based on these data, there is an increasing interest in two inflammatory biomarkers, belonging to the superfamily of pentraxins, such as pentraxin 3 (PTX3) and highsensitivity C-reactive protein (hs-CRP). In this cross-sectional study, we examined a large cohort of patients with PV and ET
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