Featured Research

from universities, journals, and other organizations

Activation Of LYN Kinase Is Associated With Imatinib-resistance In CML Patients

Date:
June 24, 2008
Source:
Journal of the National Cancer Institute
Summary:
Activation of LYN kinase is associated with resistance to imatinib in patients with chronic myelogenous leukemia, researchers report.

Activation of LYN kinase is associated with resistance to imatinib (Gleevec) in patients with chronic myelogenous leukemia (CML), according to new research.

Imatinib is the standard therapy for newly diagnosed CML patients. However, some patients develop resistance to the drug over time. In some patients, resistance develops in response to mutations in the BCR-ABL gene. In other cases, though, researchers find no mutations to explain the resistance. Previous work by Nicholas Donato, Ph.D., of the University of Michigan Comprehensive Cancer Center in Ann Arbor and others suggested that one possible mechanism of this mutation-negative resistance is the activation of LYN kinase, which is normally controlled by BCR-ABL in CML cells.

In the current study, Donato and colleagues have expanded that work and examined the impact of overexpression and gene silencing of LYN kinase in CML cell lines treated with imatinib. They also determined the level of LYN activation in samples from 12 imatinib-resistant patients who lacked BCR-ABL mutations and 6 patients whose tumor cells were sensitive to the drug but who were unable to tolerate its side effects.

They found that overexpression and activation of LYN kinase was associated with imatinib resistance in both cell lines and patient samples. Moreover, when they treated these cells with imatinib, they saw that BCR-ABL activity was suppressed as happens in CML cells sensitive to the drug, but LYN activation was not suppressed. When the researchers blocked expression of the LYN gene in the resistant cells, they restored imatinib responsiveness and triggered cell death.

"These studies expand the spectrum of cellular changes that occur during imatinib therapy beyond outgrowth of cells with BCR-ABL point mutations and support the use of other tyrosine kinase inhibitors to treat a broad spectrum of imatinib-resistant CML patients," the authors write.

In an accompanying editorial, Michael Deininger, M.D., Ph.D., of the Oregon Health and Science University Cancer Institute in Portland and colleagues note that the use of primary patient samples in the current study is particularly important and provides clues as to how consistent LYN activation may occur in CML. Further elucidation of this pathway will be essential, as will surveying a larger patient sample to determine how frequently this type of resistance develops in CML patients.

"The work of [Donato and colleagues] takes us outside of the realm of thoroughly studied kinase domain mutation-based resistance and toward an improved understand¬ing of BCR-ABL--independent disease. In addition to opening new questions for exploration, these results suggest that therapies tar¬geting both BCR-ABL and LYN kinases may prove beneficial in certain circumstances of imatinib-resistant CML," the editorialists conclude.


Story Source:

The above story is based on materials provided by Journal of the National Cancer Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Wu J, Meng F, Kong L-Y, Peng Z, Ying Y, Bornmann WG, Darnay BG, et al. Association Between Imatinib-Resistant BCR-ABL Mutation-Negative Leukemia and Persistent Activation of LYN Kinase. J Natl Cancer Inst, 2008; 100:927-940

Cite This Page:

Journal of the National Cancer Institute. "Activation Of LYN Kinase Is Associated With Imatinib-resistance In CML Patients." ScienceDaily. ScienceDaily, 24 June 2008. <www.sciencedaily.com/releases/2008/06/080624174903.htm>.
Journal of the National Cancer Institute. (2008, June 24). Activation Of LYN Kinase Is Associated With Imatinib-resistance In CML Patients. ScienceDaily. Retrieved August 20, 2014 from www.sciencedaily.com/releases/2008/06/080624174903.htm
Journal of the National Cancer Institute. "Activation Of LYN Kinase Is Associated With Imatinib-resistance In CML Patients." ScienceDaily. www.sciencedaily.com/releases/2008/06/080624174903.htm (accessed August 20, 2014).

Share This




More Health & Medicine News

Wednesday, August 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: World's Oldest Man Lives in Japan

Raw: World's Oldest Man Lives in Japan

AP (Aug. 20, 2014) — A 111-year-old Japanese was certified as the world's oldest man by Guinness World Records on Wednesday. Sakari Momoi, a native of Fukushima in northern Japan, was given a certificate at a hospital in Tokyo. (Aug. 20) Video provided by AP
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) — Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
Powered by NewsLook.com
101-Year-Old Working Man Has All The Advice You Need

101-Year-Old Working Man Has All The Advice You Need

Newsy (Aug. 19, 2014) — Herman Goldman has worked at the same lighting store for almost 75 years. Find out his secrets to a happy, productive life. Video provided by Newsy
Powered by NewsLook.com
Researcher Testing on-Field Concussion Scanners

Researcher Testing on-Field Concussion Scanners

AP (Aug. 19, 2014) — Four Texas high school football programs are trying out an experimental system designed to diagnose concussions on the field. The technology is in response to growing concern over head trauma in America's most watched sport. (Aug. 19) Video provided by AP
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