RR comprises two dimeric subunits, RRM1 and RRM2, andoverexpression is believed to be a mechanism for resistance to cytotoxic nucleosideanalogs and specifically AML resistance to cytarabine.60 In addition to being an HMA, AZA has been shown to downregulate RRM2 mRNAlevels in xenograft AML mice, acting as a specific and potent RRM2 inhibitor.61 In combination, AZA with pevonedistat showed significant synergy in thetreatment of AML cell lines and AML xenografts compared to a single agent anddecreased levels of RRM2 expression.62 Here, RRM1 is linked to acute myeloid leukemia.