Interferon-Alfa2 Treatment Of Patients With Polycythemia Vera And Related Neoplasms Impacts Deregulation Of Oxidative Stress Genes And Antioxidative Defence Mechanisms. Potential Implications Of Ifn-Alfa Induced Changes In Tp53, Nrf2 And Cxcr4 For Genomic Instability And Cd34+Mobilisation

Introduction: The Philadelphia-negative myeloproliferative neoplasms are associated with chronic inflammation and accumulation of reactive oxygen species (ROS). Whole blood transcriptional profiling studies have most recently identified deregulation of several oxidative and anti-oxidative stress genes. Amongst the genes significantly downregulated is TP53 and the NFE2L2 or Nrf2 gene, the latter having a key role in the regulation of the oxidative stress response and in modulating both migration and retention of hematopoietic stem cells (HSCs). During MPN-disease progression, the HSC pool is steadily expanding with the egress of CD34+cell from stem cell niches into the circulation. In addition to Nrf2 several other genes are involved in this process, including CXCR4, which is also significantly downregulated in MPNs. Interferon-alpha2 (IFN) is recognized as a highly efficacious and promising agent in the treatment of MPNs. Taken into account that chronic inflammation with ROS accumulation is likely involved in the pathogenesis of MPNs, ultimately implying the induction of an altered redox balance of pivotal significance for stem cell mobilization in MPNs, we herein report the first study on the impact of IFN upon oxidative stress and anti-oxidative defence genes.