The methyltransferase activity of NSD1 is retained in the NUP98-NSD1 fusion, and gives rise to abnormally high levels of H3K36 methylation, enforcing activation of transcription of oncogenes such as HOXA9. As in MLL-R leukemia, elevated expression of HOXA9 in AML harboring NUP98-NSD1 blocks differentiation of blood cell progenitors, leading them to acquire the capacity for unlimited self-renewal and malignant transformation (Wang et al., 2007). This evidence concerns the gene KMT2A and acute myeloid leukemia.