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

Fingerprint

Primary Myelofibrosis
C-Reactive Protein
Alleles
Phenotype
Mutation
Odds Ratio
Splenomegaly
Glucocorticoid Receptors
Lymphocyte Activation
Platelet Count
Leukocyte Count
Haplotypes
Disease Progression
Anemia
Logistic Models
Demography
Inflammation
Incidence

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

@article{63295dafb4654b438eff79cffc8e53d8,
title = "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",
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.",
keywords = "46/1 haplotype, A3669G polymorphism, ASXL1, C-reactive protein, CALR, EZH2, Inflammation, JAK2V617F, MPL, Myelofibrosis",
author = "Giovanni Barosi and Margherita Massa and Rita Campanelli and Gabriela Fois and Paolo Catarsi and Gianluca Viarengo and Laura Villani and Valentina Poletto and Tiziana Bosoni and Umberto Magrini and Gale, {Robert P.} and Vittorio Rosti",
year = "2017",
month = "9",
day = "1",
doi = "10.1016/j.leukres.2017.06.004",
language = "English",
volume = "60",
pages = "18--23",
journal = "Leukemia Research",
issn = "0145-2126",
publisher = "Elsevier Ltd",

}

TY - JOUR

T1 - Primary myelofibrosis

T2 - Older age and high JAK2V617F allele burden are associated with elevated plasma high-sensitivity C-reactive protein levels and a phenotype of progressive disease

AU - Barosi, Giovanni

AU - Massa, Margherita

AU - Campanelli, Rita

AU - Fois, Gabriela

AU - Catarsi, Paolo

AU - Viarengo, Gianluca

AU - Villani, Laura

AU - Poletto, Valentina

AU - Bosoni, Tiziana

AU - Magrini, Umberto

AU - Gale, Robert P.

AU - Rosti, Vittorio

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

KW - 46/1 haplotype

KW - A3669G polymorphism

KW - ASXL1

KW - C-reactive protein

KW - CALR

KW - EZH2

KW - Inflammation

KW - JAK2V617F

KW - MPL

KW - Myelofibrosis

UR - http://www.scopus.com/inward/record.url?scp=85020702184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020702184&partnerID=8YFLogxK

U2 - 10.1016/j.leukres.2017.06.004

DO - 10.1016/j.leukres.2017.06.004

M3 - Article

C2 - 28622624

AN - SCOPUS:85020702184

VL - 60

SP - 18

EP - 23

JO - Leukemia Research

JF - Leukemia Research

SN - 0145-2126

ER -