Featured Research

from universities, journals, and other organizations

New Strategy For Treating Chronic Myelogenous Leukemia

Date:
January 18, 2007
Source:
Virginia Commonwealth University
Summary:
Virginia Commonwealth University Massey Cancer Center researchers have identified an approach to enhance the activity of a new anti-cancer agent that has already shown impressive efficacy in the treatment of chronic myelogenous leukemia.

Virginia Commonwealth University Massey Cancer Center researchers have identified an approach to enhance the activity of a new anti-cancer agent that has already shown impressive efficacy in the treatment of chronic myelogenous leukemia.

Chronic myelogenous leukemia, or CML, is a cancer of the bone marrow caused by a specific genetic abnormality and is one of the more common forms of leukemia. Imatinib mesylate (Gleevec) is a highly effective anti-cancer agent that has revolutionized the course of therapy for patients with CML. It works by inhibiting the activity of a mutant protein, known as Bcr/ABl, which is responsible for this disease. However, despite initial success, patients eventually become resistant to imatinib mesylate.

According to Steven Grant, M.D., Massey's associate director for translational research and co-leader of the cancer center's cancer cell biology program, and senior author of the study, resistance to imatinib mesylate has prompted the development of newer generation inhibitors, such as a compound known as dasatinib, which are not only considerably more potent than imatinib mesylate, but also are active against cells expressing many of the mutations that make them resistant to the latter agent. Dasatinib also inhibits another important survival protein known as Src. However, Grant said that not all patients respond to dasatinib, and the risk remains that patients will develop resistance to this agent as well.

To address this problem, Grant and colleagues examined the effects of combining dasatinib with PD184352, another clinically relevant small molecule inhibitor of a critical cellular survival pathway that inactivates an important survival protein known as ERK1/2 (extracellular-signal regulating kinase1/2). The article was pre-published as a First Edition Paper in Blood, the journal of the American Society of Hematology, which appeared online Jan. 11.

By blocking this pathway, PD184352 reduces the survival and proliferation in numerous tumor types, including leukemia cells. The team found that combining extremely low concentrations of dasatinib with PD184352 resulted in a dramatic increase in apoptosis, or programmed cell death, in association with inactivation of multiple survival signaling pathways. Notably, enhanced lethality occurred in CML cells displaying various forms of imatinib mesylate resistance, said Grant.

"While the development of newer, more effective kinase inhibitors such as dasatinib for diseases such as CML is a clear priority, resistance of leukemia cells to these novel agents may also develop," said Grant.

"Addition of a second, targeted agent that potentiates the activity of dasatinib may reduce the leukemic burden further, and thereby reduce, or possibly even prevent the emergence of drug resistance. If validated, this concept could have significant implications for the treatment of CML and possibly other hematologic malignancies," said Grant.

This work was supported by grants from the National Institutes of Health, the Leukemia and Lymphoma Society of America and the Department of Defense.

Grant, who is also a professor of medicine and the Shirley Carter and Sture Gordon Olsson Professor of oncology, worked with a team that included: Tri K. Nguyen, Ph.D., Mohamed Rahmani, Ph.D., Hisashi Harada, Ph.D., all in the VCU Department of Medicine; and Paul Dent, Ph.D., a professor in the VCU Department of Biochemistry.


Story Source:

The above story is based on materials provided by Virginia Commonwealth University. Note: Materials may be edited for content and length.


Cite This Page:

Virginia Commonwealth University. "New Strategy For Treating Chronic Myelogenous Leukemia." ScienceDaily. ScienceDaily, 18 January 2007. <www.sciencedaily.com/releases/2007/01/070117134041.htm>.
Virginia Commonwealth University. (2007, January 18). New Strategy For Treating Chronic Myelogenous Leukemia. ScienceDaily. Retrieved September 21, 2014 from www.sciencedaily.com/releases/2007/01/070117134041.htm
Virginia Commonwealth University. "New Strategy For Treating Chronic Myelogenous Leukemia." ScienceDaily. www.sciencedaily.com/releases/2007/01/070117134041.htm (accessed September 21, 2014).

Share This



More Health & Medicine News

Sunday, September 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. 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