Featured Research

from universities, journals, and other organizations

Inhibition of CDK4 might promote lymphoma development, progression

Date:
March 20, 2014
Source:
Ohio State University Wexner Medical Center
Summary:
Anticancer agents that inhibit tumor growth by targeting a cell-cycle regulatory protein called CDK4 might actually promote the development and progression of certain B-cell lymphomas. The research suggests that CDK4 inhibitors, which are now in clinical testing, should be used cautiously, particularly in patients with B-cell lymphomas. The findings raise the possibility that these inhibitors work through off-target effects and require further investigation.

Anticancer agents that target a cell-cycle regulatory protein to inhibit tumor growth might actually promote the development and progression of certain B-cell lymphomas, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James).

The study indicates that inhibiting CDK4, a regulator of the cell cycle, promotes genetic instability and the development or progression of B-cell lymphomas that are driven by the MYC oncogene.

The research suggests that CDK4 inhibitors, which are now in clinical testing, should be used cautiously, particularly in patients with B-cell lymphomas. The findings also raise the possibility that these inhibitors work through off-target effects and require further investigation.

The study is published in the Journal of Clinical Investigation.

"Anti-CDK4 strategies are being widely tested as broad-spectrum anticancer therapies," says study leader Xianghong Zou, PhD, assistant professor of medicine and a member of the OSUCCC -- James Molecular Carcinogenesis and Chemoprevention Program. Zou's collaborators on the research included John Cleveland, PhD, professor and chair of cancer biology at The Scripps Research Institute.

"Our findings indicate that anti-CDK4 strategies must be carefully tailored because they might have unexpected lymphoma-promoting effects," Zou says.

"It was quite striking," he adds. "Silencing Cdk4 in our mouse model and in human B-cell lymphoma cells had the opposite effect of small-molecule inhibitors that are touted as selective inhibitors of CDK4 and CDK6," he says.

"Given that these agents have undergone limited profiling, it might be that these agents inhibit kinases other than CDK4, and that in lymphoma cells they promote critical factors that support cell growth and survival."

For this study, Zou and his colleagues used a mouse model of MYC-driven B-cell lymphoma they had developed earlier, and human cell lines of Burkitt and other non-Hodgkin lymphomas. Key technical findings include:

  • Although CDK4 functions as an oncogene in breast and other cancers, loss of CDK4 can greatly promote the onset and growth in a model of MYC-driven B-cell lymphoma and in human B-cell lymphoma cells;
  • The lymphoma-promoting effects of the experimental CDK4 deficiency were associated with dysregulation of a gene pathway that leads to genomic instability;
  • CDK4 deficiency leads to lymphomas with major genomic alterations that are associated with the dysregulation of genes that are known to promote cancer.

Story Source:

The above story is based on materials provided by Ohio State University Wexner Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yuanzhi Lu, Yongsheng Wu, Xiaoling Feng, Rulong Shen, Jing H. Wang, Mohammad Fallahi, Weimin Li, Chunying Yang, William Hankey, Weiqiang Zhao, Ramesh K. Ganju, Ming O. Li, John L. Cleveland, Xianghong Zou. CDK4 deficiency promotes genomic instability and enhances Myc-driven lymphomagenesis. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI63139

Cite This Page:

Ohio State University Wexner Medical Center. "Inhibition of CDK4 might promote lymphoma development, progression." ScienceDaily. ScienceDaily, 20 March 2014. <www.sciencedaily.com/releases/2014/03/140320121912.htm>.
Ohio State University Wexner Medical Center. (2014, March 20). Inhibition of CDK4 might promote lymphoma development, progression. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2014/03/140320121912.htm
Ohio State University Wexner Medical Center. "Inhibition of CDK4 might promote lymphoma development, progression." ScienceDaily. www.sciencedaily.com/releases/2014/03/140320121912.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins