Genetic variation in IL28B (IFNL3) and response to interferon-alpha treatment in myeloproliferative neoplasms

Eur J Haematol. 2018 May;100(5):419-425. doi: 10.1111/ejh.13034. Epub 2018 Mar 6.

Abstract

Objective: In myeloproliferative neoplasms (MPN), interferon-alpha (IFN-α) is an effective treatment with disease-modifying properties but currently with no clear predictors of treatment outcome. Recent genomewide association studies in chronic hepatitis C have found a strong influence of genetic polymorphism near the IL28B (IFNL3) gene in response to IFN-α treatment. In this study, we sought to evaluate the prognostic impact of IL28B rs12979860, rs8099917, and rs12980275 on IFN-α treatment response in myeloproliferative neoplasms.

Method: We retrospectively evaluated 100 patients with MPN treated with IFN-α. The hematologic treatment response on IFN-α was compared between patients and correlated with host genetic variations in IL28B. The genotypes of IL28B were determined by allelic discrimination assays.

Results: The CC genotype of rs12979860 was found significantly associated with hematologic response in polycythemia vera (PV) with a complete response (CR) in 79% (CC) compared to 48% (non-CC), (P = .036). No association between the genotypes and treatment response on hydroxyurea was found.

Conclusion: These results imply an effect of IL28B genotype on the outcome of IFN-α treatment in MPN.

Keywords: essential thrombocythemia; myeloproliferative neoplasms; polycythemia vera.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Biomarkers
  • Female
  • Genetic Association Studies
  • Genetic Variation*
  • Genotype
  • Humans
  • Hydroxyurea / administration & dosage
  • Hydroxyurea / therapeutic use
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Myeloproliferative Disorders / diagnosis
  • Myeloproliferative Disorders / drug therapy*
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / mortality
  • Prognosis
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • Interferons
  • Hydroxyurea