Featured Research

from universities, journals, and other organizations

Gene responsible for relapses in young leukemia patients

Date:
October 26, 2011
Source:
University of Montreal
Summary:
One of the causes of resistance to cancer treatment in children is now beginning to be elucidated. Acute lymphoblastic leukemia patients with a particular form of the ATF5 gene are at higher risk of having a relapse when treated with E. coli asparaginase, a key chemotherapy drug for this type of leukemia.

One of the causes of resistance to cancer treatment in children is now beginning to be elucidated. Acute lymphoblastic leukemia patients with a particular form of the ATF5 gene are at higher risk of having a relapse when treated with E. coli asparaginase, a key chemotherapy drug for this type of leukemia. This is what a study by Dr. Maja Krajinovic published in the Blood, the journal of the American Society of Hematology, reveals Dr. Krajinovic is an investigator at the Sainte-Justine University Hospital Research Center, which is affiliated with the University of Montreal.

Dr. Krajinovic's team focused on asparaginase, one of the drugs in a chemotherapy "cocktail" administered to young patients during the intensification phase of their treatment.

They observed that E. coli asparaginase therapy was associated with an increase in relapses when administered to patients who had particular polymorphism (special form) of the ATF5 gene. In fact, this gene regulates asparagine synthetase, an enzyme that produces asparagine, which in turn feeds cancer cells.

"In the presence of this polymorphism that, as we demonstrated, modifies the transcription rate of the ATF5 gene, it is possible that the medication, rather than preventing the proliferation of leukemia cells by reducing the rate of asparagine, does just the opposite by creating feedback that triggers cancer cells to produce asparagine themselves," explains Dr. Krajinovic.

The discovery of a form of gene associated with high rates of relapse during treatment with E.coli asparaginase opens the door to the possibility of selecting a type of pharmacological treatment based on a patient's genetic profile, an approach that reflects the shift toward personalized medicine. "If a DNA test detects the implicated polymorphisms in children, it will be possible to predict the risk of relapse or side effects," exclaimed Dr. Krajinovic. "The clinician can then propose an alternative treatment or adjust the dose accordingly."

Since the introduction of combination chemotherapy, the rate of pediatric survival without relapse has skyrocketed to about 80%. Yet some patients still resist treatment or present side effects. Pharmacogenetic research strategies involve studying the reaction to each drug used for combined chemotherapy based on various patient genetic profiles so as to design treatment plans that increase efficacy and reduce side effects in patients. Dr. Krajinovic has published a number of similar studies that focus on antifolate, another drug used in combination regimens to treat acute lymphoblastic leukemia.

Study Details

The study, led by Dr. Maja Krajinovic, an investigator in the Viral and Immune Disorders and Cancers research axis at the Sainte-Justine University Hospital Research Center and the Departments of Pediatrics and Pharmacology at the University of Montreal, was published online on the October 4, 2011 in the scientific journal Blood. Dr. Daniel Sinnett, an investigator working in the same research axis, conducted with Dr. Krajinovic polymorphism-related functional assays. Dr. Sinnett is also an author of many studies on the genetic determinants of acute lymphoblastic leukemia, including a recent study on natural killer cells published in collaboration with Dr. Ali Ahmad as principal author. The study was published in the August 4, 2011, issue of Blood and was reviewed in an editorial that underscored the originality of the work.

The study was funded by the Canadian Institutes of Health Research (CIHR), the Leukemia and Lymphoma Society of Canada, the Charles Bruneau Foundation and the Fondation des Gouverneurs de l'espoir. Drs. Maja Krajinovic and Daniel Sinnett also held National researcher career award from the Fonds de recherche en santι du Quιbec (FRSQ) in conjunction with this work. The functional studies were conducted in part within the context of one of the projects of Genome Quebec and Genome Canada.


Story Source:

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


Journal Reference:

  1. J. Rousseau, V. Gagne, M. Labuda, C. Beaubois, D. Sinnett, C. Laverdiere, A. Moghrabi, S. E. Sallan, L. B. Silverman, D. Neuberg, J. L. Kutok, M. Krajinovic. ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia. Blood, 2011; DOI: 10.1182/blood-2011-05-355560

Cite This Page:

University of Montreal. "Gene responsible for relapses in young leukemia patients." ScienceDaily. ScienceDaily, 26 October 2011. <www.sciencedaily.com/releases/2011/10/111026113826.htm>.
University of Montreal. (2011, October 26). Gene responsible for relapses in young leukemia patients. ScienceDaily. Retrieved April 16, 2014 from www.sciencedaily.com/releases/2011/10/111026113826.htm
University of Montreal. "Gene responsible for relapses in young leukemia patients." ScienceDaily. www.sciencedaily.com/releases/2011/10/111026113826.htm (accessed April 16, 2014).

Share This



More Health & Medicine News

Wednesday, April 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) — A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Formerly Conjoined Twins Released From Dallas Hospital

Formerly Conjoined Twins Released From Dallas Hospital

Newsy (Apr. 16, 2014) — Conjoined twins Emmett and Owen Ezell were separated by doctors in August. Now, nearly nine months later, they're being released from the hospital. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) — The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com
Cognitive Function: Is It All Downhill From Age 24?

Cognitive Function: Is It All Downhill From Age 24?

Newsy (Apr. 15, 2014) — A new study out of Canada says cognitive motor performance begins deteriorating around age 24. 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