An ineffective erythropoiesis in MDS is a result of an inflammatory environment that induces malignant clonal alterations due to: chromosomal abnormalities induced by del(5q), del(7q) deletions/additions, specific mutations of the spliceosome (SF3B1, SRSF2), transcription factors (RUNX1, ETV6) [93], NLRP3 inflammasome activation, overexpressed SMAD2/3 downstream mediators, TGF-b signaling, epigenetic modifiers (TET2, DNMT3A 5, IDH1/2, ASXL1), RNA splicing factors, all drivers of MDS pathogenesis by promoting an inhibitory activity on RBCs maturation [92,94]. Here, ASXL1 is linked to myelodysplastic syndrome.