CXCR4 and primary myelofibrosis: Fourth, defective antioxidative defence mechanisms with excessive ROS accumulation and oxidative stress – consequent to among others Nrf2 deficiency – may likely also contribute to aberrant DNA methylation [37], which has been reported in patients with MPNs [38], including hypermethylation of the CXCR4 promoter in CD34+ cells from patients with primary myelofibrosis.