Navigation Links
Activation of LYN kinase is associated with imatinib-resistance in CML patients
Date:6/24/2008

Activation of LYN kinase is associated with resistance to imatinib (Gleevec) in patients with chronic myelogenous leukemia (CML), researchers report in the June 24 online issue of the Journal of the National Cancer Institute.

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 understanding of BCR-ABLindependent disease. In addition to opening new questions for exploration, these results suggest that therapies targeting both BCR-ABL and LYN kinases may prove beneficial in certain circumstances of imatinib-resistant CML," the editorialists conclude.


'/>"/>

Contact: Liz Savage
jncimedia@oxfordjournals.org
301-841-1287
Journal of the National Cancer Institute
Source:Eurekalert

Related medicine news :

1. Pedophilia patients are found to have deficits in brain activation
2. MedCom USAs Subsidiary Card Activation Technologies, Inc.s SB2 Registration Declared Effective by SEC
3. MedCom Announces Court Rules Card Activation Technologies Patent Is Valid
4. MedCom Announces Card Activation Wins Significant Court Ruling
5. Sysmex America to Enable Prolonged Hematology Instrument Uptime for Hagerstown Medical Laboratory With 1,000th SNCS Activation
6. Data Show SuperGens Multi-Targeted Tyrosine Kinase Inhibitor Demonstrates Pre-clinical Activity in Glioblastoma Multiforme
7. ImaRx Therapeutics Submits Urokinase Data to FDA Supporting Extended Expiration Dating
8. Atypical protein kinase C stabilizes SRC-3 levels in breast cancer cells
9. EGFR protects cancer cells from starvation via a kinase-independent mechanism
10. New study shows promise in reducing surgical risks associated with surgical bleeding
11. Fluctuating eye pressure associated with visual field deterioration in glaucoma patients
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... Michigan (PRWEB) , ... June 26, 2016 , ... ... to fertility once they have been diagnosed with endometriosis. These women need a ... they also require a comprehensive approach that can help for preservation of fertility ...
(Date:6/25/2016)... Aliso Viejo, California (PRWEB) , ... June 25, 2016 , ... ... preset to fit their specific project," said Christina Austin - CEO of Pixel Film ... all fully customizable and all within Final Cut Pro X . Simply select ...
(Date:6/25/2016)... ... ... Friday, June 10, Van Mitchell, Secretary of the Maryland Department of Health and Mental ... exemplary accomplishments in worksite health promotion. , The Wellness at Work Awards took place ... BWI Marriott in Linthicum Heights. iHire was one of 42 businesses to receive an ...
(Date:6/24/2016)... ... ... June 19, 2016 is World Sickle Cell Observance Day. In an effort to ... treatments, Serenity Recovery Center of Marne, Michigan, has issued a pain management ... (SCD) is a disorder of the red blood cells, which can cause episodes of ...
(Date:6/24/2016)... ... June 24, 2016 , ... Dr. Amanda ... orthodontic treatment. Dr. Cheng has extensive experience with all areas of orthodontics, including ... accelerated osteogenic orthodontics. , Micro-osteoperforation is a revolutionary adjunct to orthodontic treatment. ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ ) ... Improvements Act of 1976, as amended ("HSR"), with respect ... Nasdaq: CPXX ) expired effective June 24, ... As previously announced on May 31, 2016, Jazz Pharmaceuticals ... which Jazz Pharmaceuticals has commenced a tender offer for ...
(Date:6/24/2016)... , June 24, 2016  Consumers have ... and regulators/payers have placed more emphasis on patient ... patient support programs in the pharmaceutical industry have ... medications. Consequently, pharmaceutical companies are focusing on becoming ... are providing products and services that improve health. ...
(Date:6/24/2016)... 2016   Bay Area Lyme Foundation , ... Center for Tick Borne Illness , Harvard Medical ... Hacking Medicine, University of California, Berkeley, and the ... five finalists of Lyme Innovation , the ... 100 scientists, clinicians, researchers, entrepreneurs, and investors from ...
Breaking Medicine Technology: