Related Experiment Video

Updated: May 8, 2026

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
09:33

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor

Published on: August 25, 2023

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

Zheng Huang1, Haiping Wu, Shannon Chuai

  • 1Authors' Affiliations: Novartis Institutes for BioMedical Research (China), Shanghai, P.R. China; Genomics Institute of the Novartis Research Foundation, San Diego, California; and Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.

Cancer Research
|August 28, 2013
PubMed

Insights

Histone methyltransferase NSD2 (WHSC1/MMSET) drives multiple myeloma growth, especially in t(4;14) cases. Targeting NSD2 offers a new therapeutic strategy for these patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Histone lysine methyltransferase NSD2 (WHSC1/MMSET) is frequently overexpressed in multiple myeloma (MM) due to the t(4;14) translocation.
  • NSD2 plays a role in myelomagenesis, indicating its potential as a therapeutic target.

Purpose of the Study:

  • To investigate the role of NSD2 methyltransferase activity in multiple myeloma cell function and tumorigenesis.
  • To elucidate the mechanism by which NSD2 contributes to MM, particularly in t(4;14)-positive cases.
  • To establish NSD2 as a therapeutic target for MM patients with t(4;14) translocations.

Main Methods:

  • In vitro studies assessing NSD2's impact on multiple myeloma cell clonogenicity, adherence, and proliferation on bone marrow stroma.
  • In vivo studies evaluating NSD2's requirement for tumorigenesis in t(4;14)+ and t(4;14)- multiple myeloma models.
  • Analysis of the role of NSD2's PHD domains in recruiting the protein to oncogenic target genes and driving transcriptional activation.

Main Results:

  • NSD2 methyltransferase activity is essential for multiple myeloma cell clonogenicity, adherence, and proliferation in vitro.
  • NSD2 is required for the tumorigenesis of t(4;14)+ multiple myeloma cells but not t(4;14)- cells in vivo.
  • The PHD domains of NSD2 are critical for its cellular activity and biological function, mediating recruitment to oncogenic targets and transcriptional activation.

Conclusions:

  • NSD2 is a key driver of multiple myeloma, particularly in cases with the t(4;14) translocation.
  • Targeting NSD2's methyltransferase activity presents a promising therapeutic strategy for multiple myeloma patients with t(4;14) translocations.
  • Understanding NSD2's mechanism of action strengthens its potential as a targeted therapy in multiple myeloma.

More Related Videos

Two Flow Cytometric Approaches of NKG2D Ligand Surface Detection to Distinguish Stem Cells from Bulk Subpopulations in Acute Myeloid Leukemia05:24

Two Flow Cytometric Approaches of NKG2D Ligand Surface Detection to Distinguish Stem Cells from Bulk Subpopulations in Acute Myeloid Leukemia

Published on: February 21, 2021

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Differentiation of Common Myeloid Progenitor Cells01:15

Differentiation of Common Myeloid Progenitor Cells

Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...