00085472can131000-sup-table_3.xlsx (450.57 kB)

Supplementary Table 3 from NSD2 Is Recruited through Its PHD Domain to Oncogenic Gene Loci to Drive Multiple Myeloma

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posted on 2023-03-30, 21:43 authored by Zheng Huang, Haiping Wu, Shannon Chuai, Fiona Xu, Feng Yan, Nathan Englund, Zhaofu Wang, Hailong Zhang, Ming Fang, Youzhen Wang, Justin Gu, Man Zhang, Teddy Yang, Kehao Zhao, Yanyan Yu, Jingquan Dai, Wei Yi, Shaolian Zhou, Qian Li, Jing Wu, Jun Liu, Xu Wu, Homan Chan, Chris Lu, Peter Atadja, En Li, Yan Wang, Min Hu

XLSX file, 450K, Gene set enrichment analysis (GSEA) reports for comparisons of PAR_TKO and active_inactive groups.

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ARTICLE 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. Cancer Res; 73(20); 6277–88. ©2013 AACR.

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Keywords

Epigenetics Hematological Cancers Myelomas Tumor Microenvironment Tumor-stromal cell interactions

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CC BY