NSD2 is recruited through its PHD domain to oncogenic gene loci to drive multiple myeloma.

TitleNSD2 is recruited through its PHD domain to oncogenic gene loci to drive multiple myeloma.
Publication TypeJournal Article
Year of Publication2013
AuthorsHuang Z, Wu H, Chuai S, Xu F, Yan F, Englund N, Wang Z, Zhang H, Fang M, Wang Y, Gu J, Zhang M, Yang T, Zhao K, Yu Y, Dai J, Yi W, Zhou S, Li Q, Wu J, Liu J, Wu X, Chan H, Lu C, Atadja P, Li E, Wang Y, Hu M
JournalCancer research
Volume73
Issue20
Pagination6277-88
Date Published2013 Oct 15
Abstract

Histone lysine methyltransferase NSD2 (WHSC1/MMSET) is overexpressed frequently in multiple myeloma due to the t(4;14) translocation associated with 15% to 20% of cases of this disease. NSD2 has been found to be involved in myelomagenesis, suggesting it may offer a novel therapeutic target. Here we show that NSD2 methyltransferase activity is crucial for clonogenicity, adherence, and proliferation of multiple myeloma cells on bone marrow stroma in vitro and that NSD2 is required for tumorigenesis of t(4;14)+ but not t(4;14)- multiple myeloma cells in vivo. The PHD domains in NSD2 were important for its cellular activity and biological function through recruiting NSD2 to its oncogenic target genes and driving their transcriptional activation. By strengthening its disease linkage and deepening insights into its mechanism of action, this study provides a strategy to therapeutically target NSD2 in multiple myeloma patients with a t(4;14) translocation.

DOI10.1158/0008-5472.CAN-13-1000
Alternate JournalCancer Res.