An Activating Mutation of the NSD2 Histone Methyltransferase Drives Oncogenic Reprogramming in Acute Lymphocytic Leukemia?

The E1099K mutation of NSD2 leads to increased dimethylation of H3K36, activating oncogenic gene expression programs. NSD2-mutant cells acquire several malignant phenotypes and demonstrate increased invasion into mouse brain parenchyma. Identification of aberrantly expressed genes and pathways provides avenues for therapeutic intervention in NSD2-dysregulated malignancy.