Featured Research

from universities, journals, and other organizations

Test could predict which children with T-cell ALL are best candidates for clinical trials

Date:
July 25, 2010
Source:
Dana-Farber Cancer Institute
Summary:
A genetic clue uncovered by scientists enables doctors to predict, for the first time, which children with T-cell acute lymphoblastic leukemia (T-ALL) are unlikely to benefit from standard chemotherapy for the disease and should therefore be among the first to receive new treatments in future clinical trials.

A genetic clue uncovered by Dana-Farber Cancer Institute scientists enables doctors to predict, for the first time, which children with T-cell acute lymphoblastic leukemia (T-ALL) are unlikely to benefit from standard chemotherapy for the disease and should therefore be among the first to receive new treatments in future clinical trials.

Related Articles


In a study in the Journal of Clinical Oncology, which will be published online on July 19, the investigators report that young people with T-ALL whose leukemia cells harbor an intact TCR-gamma gene generally have a poor response to "induction" chemotherapy -- the first course of drugs given at the time of diagnosis to spur cancer remission. Patients with this high-risk marker will be prime candidates for clinical trials in which therapies currently in development are tested.

"Even though we can cure a large subset of children with T-ALL, about 25 percent of pediatric patients with the disease die of it, either because first-line chemotherapy fails, or because they relapse after being in remission for a year or two," says the study's lead author, Alejandro Gutierrez, MD, of Dana-Farber. "Until now, there has been no way of determining ahead of time whether a patient is likely to be helped by the standard regimen of front-line drugs."

ALL, a cancer of the white blood cells, is the most common malignancy in children. T-ALL, which affects lymphocytes (lymph cells) known as T cells, accounts for about 15 percent of all pediatric ALL cases, or about 1,500 new diagnoses annually in the United States, according to the American Cancer Society.

To see if T-ALL cells contain any hints of their likelihood to resist traditional chemotherapy, investigators performed genomic tests on leukemia cells from 47 children with T-ALL, 25 of whom were long-term survivors, nine of whom failed to achieve complete remission after induction chemotherapy, and 13 who relapsed after going into remission. The molecular test, known as comparative genomic hybridization, probes thousands of genes to see if any are present in unusual quantities in the cells.

"We found that patients whose cells did not have rearranged DNA in the TCR-gamma gene were the most likely to fail induction therapy," Gutierrez says. "Of the 47 samples studied, eight had this particular high-risk marker. Six of those patients did not respond to first-line chemotherapy."

Tumor samples from patients whose disease relapsed after going into remission were found to have TCR-gamma rearrangements at the time of diagnosis. In some of these patients, however, rearrangements were not found after relapse. Researchers believe that such patients almost certainly had a small number of leukemia-initiating cells without rearrangements at diagnosis, but in quantities too small for detection, says the study's senior author, Thomas Look, MD, of Dana-Farber. After the DNA-rearranged cells died in response to chemotherapy, the remaining chemo-resistant cells came to predominate.

Other molecular studies are giving scientists leads as to which genes and gene pathways are responsible for the ability of some T-ALL cells to defy conventional chemotherapy, notes Gutierrez. Some of these genes are known to be targeted by drugs currently being studied in clinical trials for other diseases, raising the possibility that they might be effective for certain T-ALL patients as well.

"Given the relatively high failure rate of conventional induction therapy for this disease, there is an urgent need to test alternative chemotherapy agents in patients," Gutierrez remarks. "Routine testing for rearrangements in TCR-gamma," which could be accomplished fairly inexpensively with a standardized test, "would enable us to identify which patients could gain the most benefit from these agents."

The research was supported by grants from the National Institutes of Health, the William Lawrence Foundation, and the Community Foundation of the National Capital Region.

Co-authors of the study include Suzanne Dahlberg, PhD; Donna Neuberg, ScD; Jianhua Zhang, PhD; Ruta Grebliunaite, Takaomi Sanda, MD PhD; Alexei Protopopov, PhD; Jeffrey Kutok, MD, PhD; Lewis Silverman, MD; Lynda Chin, MD; and Stephen Sallan, MD, Dana-Farber; Valeria Tosello, PhD, and Adolfo Ferrando, MD, PhD, Columbia University, New York; Richard Larson, MD, PhD, and Stuart Winter, MD, University of New Mexico, Albuquerque; Michael Borowitz, MD, PhD, Johns Hopkins University, Baltimore; Mignon Loh, MD, University of California San Francisco; Charles Mullighan, MD, St. Jude Children's Research Hospital, Memphis, Tenn.; and Stephen Hunger, MD, University of Colorado, Denver.


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Cite This Page:

Dana-Farber Cancer Institute. "Test could predict which children with T-cell ALL are best candidates for clinical trials." ScienceDaily. ScienceDaily, 25 July 2010. <www.sciencedaily.com/releases/2010/07/100719162635.htm>.
Dana-Farber Cancer Institute. (2010, July 25). Test could predict which children with T-cell ALL are best candidates for clinical trials. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2010/07/100719162635.htm
Dana-Farber Cancer Institute. "Test could predict which children with T-cell ALL are best candidates for clinical trials." ScienceDaily. www.sciencedaily.com/releases/2010/07/100719162635.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com
WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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