Research paperPrimary myelofibrosis: Older age and high JAK2V617F allele burden are associated with elevated plasma high-sensitivity C-reactive protein levels and a phenotype of progressive disease

•We have measured plasma levels of hs-CRP in 526 subjects with PMF.•38% of subjects with PMF had elevated hs-CRP.•Age ≥ 52 years and JAK2V617F mutation with ≥ 50% allele burden were independently associated with elevated hs-CRP.•Older age and high allele burden JAK2V617F mutation were also associated with a phenotype of progressive disease.•We interpreted our finding as reflecting an intrinsic inflammatory pathway promoted by older age and high allele burden JAK2V617F.

We measured plasma levels of high-sensitivity C-reactive protein (hs-CRP) in 526 subjects with primary myelofibrosis (PMF). Thirty-eight percent had an elevated hs-CRP level (≥ 0.3 mg/dL). Elevated hs-CRP levels were associated with a progressive disease phenotype, including anemia, high white blood cell count, low platelet count, increased splenomegaly, increased risk of blast transformation, and worse survival. Age ≥ 52 years, but no other demographic characteristics, was associated with an elevated hs-CRP level in multivariable logistic regression (odds ratio [OR], 4.29; 95% CI, 2.73-6.77; P < 0.001). Subjects with JAK2V617F mutation and an allele burden ≥ 50% had an age-independent higher incidence of elevated hs-CRP level (OR = 1.97; 95% CI,1.21-3.22; P = 0.006) compared with a combined cohort of subjects with JAK2V617F <50% allele burden, CALR, MPL mutations, or no detectable driver mutations. Neither ASXL1 or EZH2 sub-clonal mutations, nor JAK2 46/1 haplotype or the A3669G polymorphism of glucocorticoid receptor were significantly associated with increased hs-CRP levels. Subjects with age ≥ 52 years and JAK2V617F with ≥ 50% allele burden had a phenotype of progressive disease. Our data indicate that older age and high JAK2V617 allele burden are major determinants of inflammation in PMF, and are associated with disease progression.