ArrayExpress Uploader0humanNSD2 knockoutNSD2 knockoutNSD2 knockoutGene expression profiling of the KMS11 cellsGene expression profiling of the KMS11 cellsGene expression profiling of the KMS11 cellsWT NSD2 and MMSET I isoformWT NSD2 and MMSET I isoformWT NSD2 and MMSET I isoformWT NSD2WT NSD2WT NSD2catalytic dead mutant (CDM) NSD2 and MMSET I isoformcatalytic dead mutant (CDM) NSD2 and MMSET I isoformcatalytic dead mutant (CDM) NSD2 and MMSET I isoformcatalytic dead mutant (CDM) NSD2catalytic dead mutant (CDM) NSD2catalytic dead mutant (CDM) NSD2NSD2 MMSET I isoformNSD2 MMSET I isoformNSD2 MMSET I isoformNSD2 H762Y mutationNSD2 H762Y mutationNSD2 H762Y mutationNSD2 526-1365NSD2 526-1365NSD2 526-1240NSD2 526-1240NSD2 526-1365NSD2 526-12402315arrayexpress_sid4NSD2, a histone lysine methyltransferase, is overexpressed as a result of the t(4;14) translocation that is associated with 15-20% of...E-GEOD-50072/profile/8773/arrayexpressuploader130bonebone marrowcelldiseasegenomehistonelysinemultiple myelomamyelomaproteinstromaDec.12, 2014Falsegene-expression-profiling-of-kms11-parental-par-tkE-GEOD-50072_A-AFFY-44Gene expression profiling of KMS11 parental (PAR), TKO and 8 reconstituted linesJul.12, 2014NSD2, a histone lysine methyltransferase, is overexpressed as a result of the t(4;14) translocation that is associated with 15-20% of multiple myeloma. Earlier studies have indicated that NSD2 may be involved in myelomagenesis and suggested that it may be a target for myeloma therapy. Here we show that NSD2 is required for clonogenic growth, adherence and proliferation on bone marrow stroma, and tumorigenesis of t(4;14)+ but not t(4;14)- myeloma cells, in a methyltransferase activity dependent manner. Furthermore, we found that PHD domains are important for NSD2 cellular activity and biological functions by recruiting it to oncogenic gene loci and driving downstream transcription activation events. These results strengthened the disease link of NSD2 and provided a basis that targeting NSD2 may be a therapeutic strategy in multiple myeloma patients with t(4;14) translocation. Our data also revealed multiple domains in the protein for possible chemical modulation. To elucidate the mechanisms underlying the oncogenic potential of NSD2 in myeloma, we performed microarray analysis on KMS11 parental (PAR), TKO and 8 reconstituted lines. Based on the whole-genome expression profile, the 10 samples clearly fell into 4 clusters – (1) PAR; (2) TKO; (3) WT, WT+MMSET I, 526-1240 and 526-1365; and (4) CDM, CDM+MMSET I, MMSET I and H762Y Biological triplicates of cell cultures of indicated lines were harvested in TRIzol (Invitrogen) and characterized by human U133 plus 2.0 Affymetrix GeneChip. The gene expression data was normalized using the Robust Multiarray Averaging (RMA) method and log2 transformed before comparisons.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-50072http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-50072/samples/