Taking into account the oncogenic role of MDM2 reported in del(5q) MDS and AML, we further propose a functional switch of MDM2 from oncogenic to tumor suppressive during HMA resistance, with loss of MDM2 being attributed to RNA hypomethylation (Figure 5) [50,51] In addition, the truncated MDM2 observed in our study only retains the 3′ UTR and is in-keeping with a long non-coding RNA without open reading frame [55]. Here, MDM2 is linked to myelodysplastic syndrome.