AI Article Synopsis
- Chromosome band 9p24 is often amplified in primary mediastinal B cell lymphoma (PMBL) and Hodgkin lymphoma (HL), indicating it may play a key role in these cancers.
- Researchers identified the oncogenes JAK2 and JMJD2C as critical players in the survival of these lymphomas using an RNA interference library.
- Inhibiting JAK2 and JMJD2C together disrupts key phosphorylation and methylation processes, leading to increased repressive chromatin and decreased MYC expression, suggesting potential for targeted therapies in PMBL and HL.
Article Abstract
Chromosome band 9p24 is frequently amplified in primary mediastinal B cell lymphoma (PMBL) and Hodgkin lymphoma (HL). To identify oncogenes in this amplicon, we screened an RNA interference library targeting amplicon genes and thereby identified JAK2 and the histone demethylase JMJD2C as essential genes in these lymphomas. Inhibition of JAK2 and JMJD2C cooperated in killing these lymphomas by decreasing tyrosine 41 phosphorylation and increasing lysine 9 trimethylation of histone H3, promoting heterochromatin formation. MYC, a major target of JAK2-mediated histone phosphorylation, was silenced after JAK2 and JMJD2C inhibition, with a corresponding increase in repressive chromatin. Hence, JAK2 and JMJD2C cooperatively remodel the PMBL and HL epigenome, offering a mechanistic rationale for the development of JAK2 and JMJD2C inhibitors in these diseases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049192 | PMC |
| http://dx.doi.org/10.1016/j.ccr.2010.11.013 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!