GSTM1 and sickle cell disease: RRx-001 treatment of human RBCs induces a senescent-like state in RBCs that promotes adhesiveness via the exposure of PS; the mechanism for this involves RRx-001 binding to the Cys93 residue of hemoglobin (Hb), and inducing oxidation of Hb that then stimulates exposure of PS to the outer bilipid leaflet, as occurs for instance in sickle cell disease [17,75] and in the vesiculation and clearance of senescent red blood cells.