Navigation Links
A new target for lymphoma therapy
Date:12/9/2009

Researchers at the Program in Cellular and Molecular Medicine and the Immune Disease Institute at Children's Hospital Boston (PCMM/IDI) have found a link between a common mutation that can lead to cancer and a distant gene regulator that enhances its activity. Discovery of this relationship could lead to drugs targeting B-cell lymphomas, including Burkitt's lymphoma, an aggressive cancer in children, as well as multiple myelomas and other blood-related cancers.

Lymphomas often originate in B cells, the same cells that produce antibodies to help fight infections. A B cell can become cancerous if a gene known as c-myc leaps to another section of DNA (the IgH region, responsible for building antibodies), fuses with it, and somehow becomes over-activated. Scientists have wondered for years how this oncogenic activation occurs, in particular what component in the IgH region activates c-myc. The new study, published in the Dec. 10 issue of Nature, identifies this regulatory component, and marks the first time researchers are able to understand how this movement of genes, or "chromosomal translocation," can hijack a B cell's operation badly enough to lead to cancer.

"IgH-to-myc translocation is the classic example of activation of an oncogene in cancer," says Frederick Alt, PhD, scientific director of PCMM/IDI and senior author of the study. "But nobody really understood how it works."

Aberrant DNA translocations can occur during two different stages of a B cell's development: during a process known as VDJ recombination, when a progenitor B cell creates an antibody to fight a specific pathogen, or during class switch recombination, when a mature B cell gives its antibody a different strategy to fight infection (changing from an IgM to an IgG antibody, for example). Based on their past research , Alt and his colleagues decided to focus on one part of the IgH region called IgH 3' regulatory region (IgH3'RR). They had already shown IgH3'RR to be a far-reaching gene regulator that enhances the transcription of neighboring genes in the IgH region during class switch recombination.

To investigate the relationship between IgH3'RR and lymphoma, the team, led by Alt and first author Monica Gostissa, PhD, of PCMM/IDI, deleted the IgH3'RR in a line of mutant mice previously generated in the Alt lab. These mice routinely develop a B-cell lymphoma in which c-myc is translocated to the IgH region of the DNA. However, without IgH3'RR, mature B cells did not become cancerous, suggesting that mature B cells -- from which most human lymphomas originate -- need IgH3'RR in order to develop into lymphoma.

"The study shows that the IgH3'RR is a key element for turning on the cancer-causing activity of c-myc after it is translocated to the IgH locus," says Alt. He noted that the study also shows that the cancer-causing activity of the IgH3'RR on c-myc can extend over surprisingly long chromosomal distances.

The study suggests the IgH3'RR as a new target for arresting lymphomas and other blood-related cancers that arise from mature B cells. Though inactivating IgH3'RR can impair a B cell's versatility in creating different classes of antibodies, it would not leave a patient immune-deficient because the B cells would retain some of their activity, says Gostissa. Furthermore, such a treatment would be reversible.

The next step is for the researchers to see what eliminating IgH3'RR will do to existing tumors, and then to create a cell-based drug screening assay to test for possible IgH3'RR inhibitors.


'/>"/>

Contact: Rob Graham
Rob.Graham@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert  

Related medicine news :

1. Potential New Target Found for Alzheimers Disease
2. Cohen Independent Research Group Issues a Buy Rating With a Target Price of $2.48 for VHGI; 8K filed regarding $50,000,000.00 Treasure Gulch Gold Reserves
3. Possible ovarian cancer treatment target identified
4. New Target May Be Eyed in Kids Brain Cancer
5. With White House Jobs Summit This Week KSBH Unveils New TV Ads Targeting Senators on Health Care
6. Alcohol companies target youths with magazine ads, new study shows
7. Targeted Breast Ultrasound Can Reduce Biopsies for Women Under Forty
8. Targeted breast ultrasound can reduce biopsies for women under 40
9. Targeted Testing Receives Favorable Reviews On PADDS, Begins Nationwide Research Study On The Target Tests of Executive Functioning-OV
10. Reportlinker Adds The Future of Senior Nutrition: Key Ingredients, Strategic Issues and Targeted Opportunities for Older Consumers
11. First live targeting of tumors with RNA-based technology
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
A new target for lymphoma therapy
(Date:12/9/2016)... ... December 09, 2016 , ... The American Speech-Language-Hearing Association ... a critical part of public access to hearing aid technology. , ASHA emphasized ... week that, starting immediately, it would no longer enforce the requirement that ...
(Date:12/9/2016)... ... December 09, 2016 , ... "I have gout, and I wanted to ... recipe, which is meant to relieve gout and pain caused by varicose veins. I ... boost every time. It relieved what VA doctors called the worst sinusitis case they'd ...
(Date:12/9/2016)... ... December 09, 2016 , ... Mediaplanet today announces distribution of the latest edition ... to sign up as an organ donor for the 123,000 people in the United ... donor can save up to 8 saves through organ donation and enhance many others ...
(Date:12/9/2016)... ... December 09, 2016 , ... The Pennsylvania Athletic ... (PCN) during the summer of 2016. The program was made possible by a ... States Department of Health and Human Services Administration. The broadcast, Use Your ...
(Date:12/8/2016)... ... December 08, 2016 , ... ... LLC, announced the first national #QuackGivesBack campaign which supported local breast cancer organizations ... first franchise-wide Quack Gives Back initiative, and we’re very pleased with ...
Breaking Medicine News(10 mins):
(Date:12/8/2016)... , Dec. 8, 2016 Global ... report on the global interventional radiology market analyzes ... The report comprises an elaborate executive summary, including ... various segments and sub-segments. The research is ... research formed the bulk of our research efforts ...
(Date:12/8/2016)... -- Eli Lilly and Company (NYSE: LLY ) ... trial at the 9 th Clinical Trials on ... not meet the primary endpoint in the EXPEDITION3 clinical ... mild dementia due to Alzheimer,s disease (AD), and Lilly ... treatment of mild dementia due to AD. ...
(Date:12/8/2016)... Dec. 8, 2016 Bodycad announced it ... improving the accuracy, reproducibility and speed for 3D ... and small bone orthopaedic applications. These patents are ... personalized orthopaedic restorations based on each patient,s distinct ... the company harnesses the world,s first suite of ...
Breaking Medicine Technology: