Influence of interferon-α treatment outcome in polycythemia vera and essential thrombocythemia by genetic polymorphism in IL28B

Background: Interferon-α (IFN-α) is a therapeutic option in high risk patients with Myeloproliferative Neoplasms (MPNs). The response to IFN-α treatment of chronic hepatitis C was shown to be strongly influenced by several related single nucleotide polymorphisms (SNP) in a region adjacent to the IL28B gene. The objective of this study was to investigate the possibility of similar influence of IL28B gene polymorphism in IFN-α treated MPN patients. Methods: 20 patients with polycythemia vera (PV) or essential thrombocythemia (ET) treated with IFN-α included, 7 were earlier treated with hydroxyurea. Hematologic response was evaluated using the European Leukemia Net (ELN) criteria. DNA from whole blood samples was isolated using MagNA Pure LC DNA Isolation Kit I for IL28B genotyping, and the variability at rs12979860, rs12980275 and rs8099917 were determined by allelic discrimination assays using Taqman minor groove binding probes. Results: The IFN-α treatment reduced platelet count (p<0.05), and in patients with polycythemia vera (PV) also hemoglobin, hematocrit and white blood cell counts declined (p<0.05). Hematologic response by ELN criteria was significantly influenced by the IL28B SNP. Among 20 patients with PV or ET, the CC genotype at rs12979860 was found in 8/11 patients (73%) with hematologic CR as compared with 1/9 (11%) with PR or NR (p=0.010). Conclusion: The results in this pilot study indicate that variation in IL28B genotype might influence hematologic response in IFN-α treated MPN patients.