PU.1 overexpression leads to differentiation blocks and thus acute erythroleukemia (101), but the reduction of PU.1 expression (and consequently gene network) has been shown to aid in leukemic transformation by many mechanisms including TET2 deficiency (253, 254), differentiation blocks and cellular expansion involving synergistic combination of PRC2 and HDAC1 (255), and at the post-transcriptional level, sustained expression of miR-155 (256). Here, SPI1 is linked to acute erythroid leukemia.