Authors: I. Olkhovskiy∗, M. Stolyar, A. Gorbenko, D. Lagutinskaya, E. Dunaeva, K. Mironov, G. Shipulin, T. Olkhovik, M. Mikhalev, E. Vasiliev, M. Smelyanskaya, A. Hazieva
Published: 2019-06-17
DOI: 10.1097/01.hs9.0000564140.13072.99
Source: Full article
Background:Interferon‐α (IFN‐α) provides several benefits to myeloproliferative neoplasms (MPNs) patients and leads 35% of its experienced a good molecular response. Both newly diagnosed and previously treated patients with polycythemia vera (PV) exhibit high hematologic response rates, and some of these patients achieve molecular responses [Kiladjian J‐J., et al., 2016]. Nevertheless, IFN‐α therapy is often accompanied by serious side effects, which forces some patients to refuse treatment. Only one scientific team [Lindgren M., et al., 2012, 2018] previously published data demonstrating the effect of IL28B gene polymorphisms on the success of interferon therapy in MPNs.Aims:Evaluate the prognostic impact of IL28B rs12979860 and rs8099917 on IFN‐α treatment response and toxicity in patients with MPNs.Methods:35 patients were investigated: 18 with polycythemia vera, 12 with essential thrombocythemia and 5 with primary myelofibrosis. All patients were treated with IFN‐α (three times weekly). DNA from whole blood samples was isolated using «DNAsorb‐B» (Central Research Institute for Epidemiology, Russia). The rs12979860 and rs8099917 SNPs genotyping was determined by pyrosequencing on a PyroMark Q24 instrument. Allele burden JAK2 V617F was determined using «Myeloscreen JAK2» («Formula of gene Ltd», Russia). Hematologic response was evaluated using the European Leukemia Net criteria. The quantitative values are given as a median and 25% and 75% percentiles.Results:The JAK2 V617F allele burden after 60 months of IFN‐α therapy was significantly reduced in samples of patients with polycythemia vera in the presence of a “strong” TT/CC variant of the haplotype IL28B (13; 8.4–24.4) compared with other variants of polymorphism of these gene (57; 44,3–67,0). The average duration of therapy to failure due to side effects of IFN‐α was also 2–3 times shorter (p < 0.05) in patients with a TT/CC haplotype. The therapeutic impact of IFN‐α in patients with MPN involve IL28B signaling pathways. This is the second independent confirmation of the data by Lindgren et al.Summary/Conclusion:Genotype evaluation of IL28B can be useful for predicting the effectiveness of interferon therapy in MPNs.image