PHF8 and acute promyelocytic leukemia: For example, in APL, a UTX–NCoA6–ASH2L–PML/RARα complex is essential for APL cell differentiation upon RA treatment via H3K4 methylation, H3K27 demethylation, and the consequent transcriptional activation of RAR target genes.148 Similarly, PHF8, as a coactivator, is recruited by RARα fusions to activate the expression of their downstream targets.