The aberrant increase in NSD2 expression observed in patients with multiple myeloma is attributed to the t(4,14) translocation,[58, 59] while NSD2 methyltransferase hyperactivity in pediatric patients with acute lymphoblastic leukemia is the result of the substitution of glutamic acid with lysine at residue 1099 in its SET structural domain (p. Glu1099Lys and p. E1099K), which in turn leads to tumorigenesis and progression.[60, 61, 62] In addition, NSD2 upregulation involves chromatin remodeling, aberrant regulation of transcription factors, and abnormal histone modifications. Here, NSD2 is linked to acute lymphoblastic leukemia.