Here, we found that oTR suppressed STAT3 activation in oTR-induced AML differentiation therapy, while it induced the activation of STAT1; moreover, oTR induced the regulation of transcription factors C/EBPα, C/EBPβ, and PU.1, all of which are important during myeloid differentiation. Here, SPI1 is linked to acute myeloid leukemia.