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

Journal article
Authors Marie Lindgren
Jan Samuelsson
Lars Nilsson
Håvar Knutsen
Waleed Ghanima
Johan Westin
Peter L Johansson
Björn Andréasson
Published in European journal of haematology
Volume 100
Issue 5
Pages 419-425
ISSN 1600-0609
Publication year 2018
Published at
Pages 419-425
Language en
Links dx.doi.org/10.1111/ejh.13034
www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Adolescent, Adult, Aged, Alleles, Biomarkers, Female, Genetic Association Studies, Genetic Variation, Genotype, Humans, Hydroxyurea, administration & dosage, therapeutic use, Interferon-alpha, administration & dosage, adverse effects, therapeutic use, Interleukins, genetics, Male, Middle Aged, Mutation, Myeloproliferative Disorders, diagnosis, drug therapy, genetics, mortality, Prognosis, Retrospective Studies, Treatment Outcome, Young Adult
Subject categories Internal medicine

Abstract

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

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