The current study examined the role of SETBD1 in modulating the transcription of PAF1c target genes Hoxa9 and Meis1. Due to the important role of Hoxa9 and Meis1 in development, normal hematopoiesis, and hematologic malignancies like AML, the interaction between SETDB1 and the PAF1c has major implications on our understanding of the regulation of these genes and the potential to therapeutically target these epigenetically regulated pathways. The gene discussed is SETDB1; the disease is acute myeloid leukemia.