Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

ALL survivors bear genetic damage from life-saving chemotherapy

01.07.2004


Children who undergo chemotherapy and survive acute lymphocytic leukemia (ALL) endure a 200-fold increase in the frequency of somatic mutations in their DNA, researchers from the University of Vermont Medical School reported in the July 1 issue of the journal Cancer Research. The alterations in the children’s gene sequence remain embedded within their chromosomes and may pose elevated risk for development of second malignancies and other diseases later in life, cautioned Barry A. Finette, M.D., Ph.D., associate professor of pediatrics at the University of Vermont.

"The treatments that are used to help children defeat this disease are keeping a very large percentage of them alive," Finette said. "Pediatricians are continually monitoring these children as they live beyond five, ten, and more recently, 15 years after their ALL is in remission. We now need to be proactive about studying any long term genetic ramifications that these children may face due to the treatment therapy they endured during their bout with cancer." Finette noted that children who are cured of ALL after chemotherapy have a 5-20 times greater risk of developing secondary malignant neoplasm’s as well as other complications. Subsequent illnesses may be associated with increased changes in the patient’s genes resulting from their treatments during ALL therapy.

Finette and his team of scientists examined the frequencies of alterations found within a marker gene in the blood cells of ALL patients at four intervals, between the time they were diagnosed until after they had completed their treatments. By examining the number of T cells in the patients’ blood that contained mutations in the HPRT reporter gene, the researchers estimated how frequently chemotherapy altered the DNA sequence within that specific marker gene.



The research showed that at the time of diagnosis, the blood of patients contained an average of 1.4 cells with HPRT mutations out of every million T cells, Finette said. The treatment for ALL consists of a three-phase regimen, including induction, consolidation and maintenance. By the time the patients completed their consolidation phase of treatment, an average of 52 T cells per million cells contained HPRT mutations. By the final stage of treatment, an average of 93 of every million T cells had mutations in HPRT. After treatment was stopped, an average of 271 of every million T cells contained HPRT mutations, more than a 200-fold increase.

The study included 45 children with ALL who averaged 5.5 years of age at time of diagnosis. The number of HPRT mutations found in the patients at the time of diagnosis did not differ from healthy children of the same age, the researchers reported. The increase in genetic mutations seen in the ALL patients accumulated over the course of their treatments.

"The mutations that arise during treatment for ALL remained elevated after completion of therapy," Finette noted. But in the absence of the mutagenic chemotherapy, the rate of further genetic damage subsided. The post-treatment rate of HRPT mutations in the ALL survivors paralleled the number of new gene alterations observed in healthy children of similar age.

The chemical therapeutics administered to the patients, however, are powerful, and while they are designed to keep cancer cells from proliferating and to induce cancer cell death, normal cells can also be affected.

"The therapies used to assist these children overcome ALL have the potential to cause genetic damage to many different cell populations in their rapidly growing bodies," Finette said. "Because they have larger numbers of replicating cell populations during their growth and development stages than adults have, they are more susceptible than adults to effects of the chemotherapies genotoxicity."

ALL is the most common pediatric malignancy, but many ALL patients respond well to chemotherapeutic interventions. Since the 1960s, the five-year survival rate for children with ALL has increased to almost 80 percent. Patient remission and long-term survival is credited to the development of national standardized chemotherapeutic treatment protocols. More than 70 percent of ALL children less than 20 years of age, and 85 percent of children less than 15 years old participate in the standardized ALL chemotherapy treatment regimes.

"Because of the effectiveness of the treatment employed today, we are able to give many more children a chance for a long life without cancer," Finette said. "Our studies are aimed at enabling us to better understand further challenges that we may face in keeping these patients healthy as they get 10, 15 or more years out from overcoming ALL."

Russell Vanderboom | EurekAlert!
Further information:
http://www.aacr.org

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

On the way to developing a new active ingredient against chronic infections

21.08.2017 | Life Sciences

Smart Computers

21.08.2017 | Information Technology

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>