A3669G polymorphism of glucocorticoid receptor is a susceptibility allele for primary myelofibrosis and contributes to phenotypic diversity and blast transformation

Valentina Poletto, Vittorio Rosti, Laura Villani, Paolo Catarsi, Adriana Carolei, Rita Campanelli, Margherita Massa, Myriam Martinetti, Gianluca Viarengo, Alberto Malovini, Anna Rita Migliaccio, Giovanni Barosi

Research output: Contribution to journalArticlepeer-review

Abstract

The frequency of A3669G single nucleotide polymorphism (SNP) of human glucocorticoid receptor has been reported increased in polycythemia vera. We investigated the frequency ofA3669G SNP and its impact on disease phenotype and progression in 499 patients with primary myelofibrosis (PMF). The distribution of the A3669G allele differed between PMF patients and 2 healthy control populations (odds ratio, 1.6 and 1.8). The variant allele at the homozygous state (G/G) was associated with higher white blood cell count, larger spleen index, and higher frequency of circulating CD34+ cells at diagnosis. The latter association remained significant after correction for the JAK2 V617F genotype. In patients JAK2V617F mutated, the G/G genotype was associated with shorter overall survival (77.6 months vs 298 months, P = .049) and blast transformation (BT)- free survival (76.7 months vs 261 months; P = .018). The latter association remained significant after correction for the known BT risk factors, such as age, sex, white blood cell count, percentage of blasts, IPSS prognostic score, and homozygosity for JAK2V617F (hazard ratio = 3.3; P = .006). In conclusion, the glucocorticoid receptor A3669G is a susceptibility allele for PMF: it contributes to confer the phenotype of excess myeloproliferation, and it cooperates with the JAK2V617F mutation in determining BT.

Original languageEnglish
Pages (from-to)3112-3117
Number of pages6
JournalBlood
Volume120
Issue number15
DOIs
Publication statusPublished - Oct 11 2012

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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