Primary 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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)18-23
Number of pages6
JournalLeukemia Research
Volume60
DOIs
Publication statusPublished - Sep 1 2017

Keywords

  • 46/1 haplotype
  • A3669G polymorphism
  • ASXL1
  • C-reactive protein
  • CALR
  • EZH2
  • Inflammation
  • JAK2V617F
  • MPL
  • Myelofibrosis

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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