HES1 and acute lymphoblastic leukemia: Aberrantly activated NOTCH1 in T-ALL binds to the promoter of HES1, a critical mediator of leukemogenesis [67], and forces considerable eviction of EZH2 and other PRC2 subunits as well as loss of H3K27 tri-methylation repressive marks [46], reinforcing the activation of HES1.