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NSD2 as a Promising Target in Hematological Disorders
1Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (CSIC-Universidad Autónoma de Madrid), 28049 Madrid, Spain.
Abstract:
Alterations of the epigenetic machinery are critically involved in cancer development and maintenance; therefore, the proteins in charge of the generation of epigenetic modifications are being actively studied as potential targets for anticancer therapies. A very important and widespread epigenetic mark is the dimethylation of Histone 3 in Lysine 36 (H3K36me2). Until recently, it was considered as merely an intermediate towards the generation of the trimethylated form, but recent data support a more specific role in many aspects of genome regulation. H3K36 dimethylation is mainly carried out by proteins of the Nuclear SET Domain (NSD) family, among which NSD2 is one of the most relevant members with a key role in normal hematopoietic development. Consequently, NSD2 is frequently altered in several types of tumors-especially in hematological malignancies. Herein, we discuss the role of NSD2 in these pathological processes, and we review the most recent findings in the development of new compounds aimed against the oncogenic forms of this novel anticancer candidate.
Insights
Nuclear SET Domain (NSD) 2 alterations are key in cancer, particularly hematological malignancies. This review covers NSD2
Area of Science:
- Epigenetics
- Cancer Biology
- Molecular Oncology
Background:
- Epigenetic modifications, such as Histone 3 Lysine 36 dimethylation (H3K36me2), are crucial in cancer development.
- H3K36me2, primarily mediated by Nuclear SET Domain (NSD) proteins, plays a significant role in genome regulation.
- NSD2 is vital for hematopoietic development and frequently altered in hematological malignancies.
Purpose of the Study:
- To discuss the role of NSD2 in cancer, especially hematological malignancies.
- To review recent findings on NSD2 as an anticancer target.
- To highlight the development of novel compounds targeting oncogenic NSD2.
Main Methods:
- Literature review of studies on NSD2 function in cancer.
- Analysis of recent research on NSD2 alterations in hematological malignancies.
- Compilation of data on emerging therapeutic compounds targeting NSD2.
Main Results:
- NSD2 alterations are implicated in the development and maintenance of various cancers.
- NSD2 plays a critical role in normal hematopoietic development.
- Specific compounds targeting oncogenic NSD2 are under active investigation.
Conclusions:
- NSD2 is a relevant target for anticancer therapies, particularly in hematological cancers.
- Targeting NSD2 offers a promising strategy for novel cancer treatments.
- Further research into NSD2-targeting compounds is warranted.
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