Navigation Links
Anchoring ABL for a better fate
Date:8/27/2013

Chronic Myelogenous Leukemia (CML) is a cancer of the white blood cells that is most commonly found in adults and in the elderly. Its incidence has been estimated to be 1 to 2 in 100,000 people. CML was the first cancer to be associated with a genetic abnormality, known as the Philadelphia Chromosome, which 95% of all CML patients carry in their cells.

The Philadelphia Chromosome is formed by exchanges of material belonging to two distinct chromosomes, number 9 and number 22. To form the Philadelphia Chromosome, these two chromosomes break at very specific places, disrupting the BCR (in chromosome 22) and the ABL (in chromosome 9) genes that were otherwise normal. Juxtaposition of these two genes in the Philadelphia Chromosome creates an abnormal kinase tyrosine known as BCR/ABL, which is an enzyme associated with cell regulation. The Philadelphia Chromosome is associated with loss of cell control and presence of immortal cells, which leads to cancer.

In the 1990s, ST1-571 (known as imatinib or Gleevec), a new inhibitor of kinase tyrosine, was developed and tested against CML cells. Since then, the drug has been used as the first line of treatment in many patients, increasing survival rates and improving patients' quality of life. However, some patients develop resistance to the drug, which has fostered development of novel drugs that act on alternative sites on the BCR/ABL enzyme.

Aiming to gain in-depth knowledge about the mechanisms involved in ABL control in normal cells, a group led by Dr. Jerson Silva at the Federal University of Rio de Janeiro, Brazil used small angle X-ray scattering, nuclear magnetic resonance, and confocal microscopy to investigate the dynamics of the entire ABL regulatory unit. The study shows that activation of the protein releases intramolecular interactions between a regulatory unit found in the N-terminal region of the ABL, the so-called N Cap, and a number of molecular modules, and pushes ABL to anchor on the cell membrane. The whole complex undergoes motions lasting micro- to milliseconds that ultimately result in the death of the cell.

The study also reveals that changes in the N-terminal region, or its absence, are associated with the entire cell escaping apoptosis, the mechanism responsible for cell death. With no apoptosis, cells become immortal and cancer strikes.

The finding has major implications for CML research as it has been known for some time that CML cells are resistant to apoptosis and that, unlike their normal counterparts, they are not found anchored to the cell membrane but loose in the cell cytoplasm. According to Guilherme A. P. de Oliveira, the first author of the study, "our findings indicate that the ABL regulatory unit is involved with the right localization of the enzyme in the cell, dictating the fate of the cell."

The results also gain further importance in the light of recent studies showing that ABL kinases have enhanced expression and activity in some solid tumors.


'/>"/>

Contact: Jerson Lima Silva
jerson@bioqmed.ufrj.br
55-212-562-6756
Publicase Comunicao Cientfica
Source:Eurekalert

Related medicine news :

1. Diet Doc Now More Closely Tailors Its Medically Supervised Diet Plans Around Individual Patient Need, Providing an Opportunity to Live Longer & Feel Better Naturally
2. MillionaireMatch.com Develops New Mobile Apps Enabling Members To Attain Better Dating Service
3. Natural Body Defense Fights Inflammation Better With Its Improved All-natural Content
4. Nursing professor receives funding to better estimate child fatalities due to abuse and neglect
5. Elena Shea’s New Book Reveals Guide to Building Vitality for Better Health
6. Pionetics® Corporation Celebrates Water Quality Month by Sharing Passion for Better Drinking Water
7. New survey of young adults: 7.8 million gained new or better coverage through Affordable Care Act
8. Golf Fitness
9. How “Power Golf Training” Helps People Get Better Physical Health to Play Golf – Vinamy
10. Flexibility Exercises
11. How “Ageless Mobility” Helps People Get Better Physical Health - Vinamy
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/24/2017)... ... May 24, 2017 , ... Adelberg-Montalvan Pediatric Dentistry ... for its patients on Long Island, New York. , Holistic dentistry puts ... is one of the biggest trends in dentistry today. , Dentist Dr. ...
(Date:5/24/2017)... Chicago, IL (PRWEB) , ... May 24, 2017 ... ... of the most prominent for-profit and nonprofit hospitals and health systems in the ... have turned around their institutions, led professional organizations and been instrumental in developing ...
(Date:5/24/2017)... ... May 24, 2017 , ... Technique, technique, technique – with ... either lifting weights for strength training and exercise or simply lifting heavy objects, advises ... “Body position is everything,” Dr. Chang says. “Improper technique in lifting anything heavy or ...
(Date:5/23/2017)... ... May 23, 2017 , ... MDLand International ... company, announced today that its iClinic V12.2 solution has achieved approval from National ... recently introduced PCMH 2017 standards which emphasize team-based care with a significant focus ...
(Date:5/23/2017)... ... May 23, 2017 , ... Allegheny Health Network and ... Joy D’Achille Center for Women’s Behavioral Health at West Penn Hospital , a ... for women suffering from pregnancy-related depression. Construction of the Center is underway with ...
Breaking Medicine News(10 mins):
(Date:5/10/2017)... 10, 2017 Radiology has become the number ... have also spiraled to the number one ranking as ... than ever before as the most complete and reliable ... with lower back pain an MRI may confirm a ... pain, resulting in entirely different treatment protocols.  In these ...
(Date:5/9/2017)... , May 9, 2017  Semler Scientific, Inc. ... technology solutions to improve the clinical effectiveness and ... for the first quarter ended March 31, 2017. ... enable our customers to identify when preventive care ... before events like heart attacks or strokes occur," ...
(Date:5/6/2017)... 5, 2017  Hill-Rom Holdings, Inc. (NYSE: HRC), has ... square feet to its Welch Allyn campus. ... to bring more than 100 new jobs to ... has maintained a significant presence for more than 100 ... positions, a large portion of which will be R&D ...
Breaking Medicine Technology: