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)... Charlotte, NC (PRWEB) , ... June 26, 2016 , ... Brent Kasmer, a legally blind ... able to be personalized through a fitness app. The fitness app plans to fix the ... solutions currently only offer a one size fits all type program , They ...
(Date:6/25/2016)... FL (PRWEB) , ... June 25, 2016 , ... The temporary closing of Bruton Memorial ... Plant City Observer , brings up a new, often overlooked aspect of head lice: the ... closing for fumigation is not a common occurrence, but a necessary one in the event ...
(Date:6/25/2016)... ... June 25, 2016 , ... Dr. Calvin Johnson has dedicated ... has implemented orthobiologic procedures as a method for treating his patients. The procedure ... doctors to perform the treatment. Orthobiologics are substances that orthopaedic surgeons use to ...
(Date:6/24/2016)... ... June 24, 2016 , ... Those who have experienced traumatic events may ... to unhealthy avenues, such as drug or alcohol abuse, as a coping mechanism. To ... for healthy coping following a traumatic event. , Trauma sufferers tend to feel a ...
(Date:6/24/2016)... ... , ... Global law firm Greenberg Traurig, P.A. announced that 20 Florida attorneys ... peers for this recognition are considered among the top 2 percent of lawyers practicing ... members of this year’s Legal Elite Hall of Fame: Miami Shareholders Mark D. ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016  Collagen Matrix, ... design, development and manufacturing of collagen and mineral ... announced today that Bill Messer has ... Marketing to further leverage the growing portfolio of ... devices. Bill joins the Collagen Matrix ...
(Date:6/24/2016)... 2016 The Academy of Managed Care Pharmacy ... that would allow biopharmaceutical companies to more easily share ... formulary and coverage decisions, a move that addresses the ... The recommendations address restrictions in the sharing ... drug label, a prohibition that hinders decision makers from ...
(Date:6/24/2016)... June 24, 2016   Pulmatrix, Inc ., (NASDAQ: ... innovative inhaled drugs, announced today that it was added ... reconstituted its comprehensive set of U.S. and global ... is an important milestone for Pulmatrix," said Chief Executive ... awareness of our progress in developing drugs for crucial ...
Breaking Medicine Technology: