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Under combined Gpx4 - and vitamin E-deficiency plasma EPO and ERFE levels increased to very high and highly significant levels (Figure 6P,Q), apparently mirroring the severity of erythropenia under combined Gpx4 - and vitamin E-deficiency.52 Taken together, the defect in reticulocyte maturation by loss of the Gpx4 gene causes ineffective erythropoiesis with simultaneous iron overload in the liver and iron-deficiency in the hematopoietic system and this phenotype is to a large part masked by vitamin E in the normal diet