High Levels Of High Sensitivity-C Reactive Protein (Hs-Crp) Are Associated With Older Age, Chromosomal Abnormalities And Jak2v617f Mutation With High Allele Burden In Primary Myelofibrosis (Pmf)

A number of evidences indicate that inflammation and deranged innate immunity intervene in the pathobiology of PMF. In this study we aimed to analyze the inflammatory components of PMF by measuring hs-CRP in a vast population of patients. hs-CRP can detect minimal variations of serum CRP levels even in the range of normal limits, and thus is a sensitive marker of low grade systemic inflammation. We included PMF patients from the data base of the Center for the Study of Myelofibrosis in Pavia with available archived plasma. We excluded patients who had been treated with disease-modifying agents at any time before or on the date of base-cohort entry (hydroxyurea, interferon, ruxolitinib, corticosteroids) and patients with acute inflammatory or autoimmune disease, malignancy, severe liver or renal dysfunction. In this study we report the results on the determinants of levels of circulating hs-CRP in PMF in an analysis in which we used parameters that could be hypothesized with a biological plausibility to influence the level of hs-CRP. Selected predictors were: age, sex, the five different genotypes reflecting the presence or absence of the driver mutations ( JAK2 V617F with low allele burden ( JAK2 V617F mutation with high allele burden (≥ 50%), CALR mutations, MPL mutations, triple negative genotype), the accessory subclonal mutations in the ASXL1 and EZH2 genes, and abnormal karyotype. 152 subjects were analyzed at diagnosis, while 353 after (median time from diagnosis, 43 months, range, 4-396 months). 86 patients (17%) had increased hs-CRP (u003e1 mg/L). The mean age of the patients was 54.4 years. Increasing age was correlated with increasing hs-CRP (R=0.45;P JAK2 V617F mutation with high allele burden (N=82) with respect to those with low allele burden (N=190) (1.09 mg/L vs. 0.46 mg/L; P JAK2 V617F allele burden and other genotypes, 29.2% in the former had increased levels of hs-CRP while it was 12.2% in the latter (P JAK2 V617F mutation, there was a significant association between the level of hs-CRP and the allele burden (R=0.12; P=0.018). Cytogenetic characteristics at diagnosis were available in 83 patients and 32 (38.5%) of them had abnormal karyotype. There was a significant difference in hs-CRP between patients bearing a chromosomal aberration and those without (mean 0.90 mg/L vs. 0.35 mg/L P=0.003). By dividing chromosomal abnormalities in unfavorable and favorable, there was no difference in hs-CRP levels between the two groups. Assay of subclonal mutations ASXL1 and EZH2 was available in 99 patients, 8.8% of them had ASXL1 mutations and 4.4% had EZH2 mutation. No difference in hs-CRP was revealed between patients bearing or not ASXL1 or EZH2 or both. We investigated the collinearity of the variables significantly associated with hs-CRP. Age was correlated with the allele burden of JAK2 V627F (R=0.18; P= JAK2 V617F allele burden, chromosomal abnormalities) is a determinant of inflammation. Disclosures No relevant conflicts of interest to declare.