Figure 3

Roles of KDMs in ATRA therapeutic response. PML–RARa forms a repressor complex with RXRa, HDACs and PRCs to inhibit the expression of myeloid differentiation-associated genes. In non-APL, LSD1 is also recruited to further remove H3K4me2/1, contributing to a more stable repressive status (not shown in figure). ATRA treatment results in a conformational change of PML–RARa, leading to dissociation of HDACs and PRCs, and recruitment of phosphorylated PHF8 to confer transcriptional activation. Activation of PHF8 by okadaic acid (OKA) may sensitise refractory APL cells to ATRA treatment.