In the present study, cellular O-GlcNAcylation was modified by using small molecule inhibition or CRISPR/Cas9 manipulation of OGA and OGT in human umbilical cord blood (UCB)-derived CD34+ HSPCs to evaluate its effect on lineage specification and erythroid maturation and in human-derived erythroblastic leukemia K562 cells that can be induced to undergo terminal differentiation with sufficient globin production. The gene discussed is OGT; the disease is acute erythroid leukemia.