Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Circles of DNA might help predict success of stem cell transplantation

08.02.2005


St. Jude study shows the level of this DNA in the blood appears to directly reflect the ability of the transplant recipient’s thymus gland to process donated stem cells and turn them into effective T cells



Measuring the quantity of a certain type of immune cell DNA in the blood could help physicians predict whether a bone marrow stem cell transplant will successfully restore a population of infection-fighting cells called T lymphocytes in a child. This research, by investigators at St. Jude Children’s Research Hospital, is published in the journal Blood.

This finding could help physicians predict whether children receiving such a transplant will experience either failure or significant delay in the reconstitution of the T cell population. Moreover, if the transplant is successful, T cells arising from donated stem cells will be available to launch attacks on the patient’s cancer cells--the so-called "graft-versus-tumor" response. This will further improve the patient’s outcome following initial therapy (chemotherapy, irradiation and surgery).


Physicians sometimes treat patients with stem cell transplants as part of therapy for a variety of diseases such as leukemia or sickle cell disease. In these cases physicians eliminate the patients’ own stem cells that produce cancerous white cells or faulty red cells and replace them with healthy stem cells from donors. If the transplants succeed, the donated stem cells repopulate the blood with healthy red and white cells.

The St. Jude team showed that the more copies of tiny rings of DNA called signal-joint TRECs (sjTRECs) there are in a child’s blood, the more likely it is that the patient’s thymus gland can act as an efficient factory where stem cells become T cells. The thymus is an immune system organ behind the breastbone that processes immature "precursor" immune cells into specialized T cells.

T lymphocytes are specialized immune cells carrying proteins called receptors on their surface. The target that a T cell recognizes and attacks depends on the makeup of its receptor, which is constructed of protein building blocks. Each protein building block is coded by a specific gene. sjTRECs form during a "mix-and-match" rearrangement of these genes into any one of countless combinations. The rings represent sections of DNA cut out of chromosomes during the mixing and matching of genes that are chosen to build a particular receptor. Each T cell uses the resulting combination of genes to make a receptor that lets the cell recognize a specific target. When stimulated to multiply, each of those cells produce an army of immune cells against their designated target.

Specific infectious organisms or other foreign substances stimulate T cells to divide and multiply in order to form an attacking army. However, the sjTRECs don’t multiply when the original T cells divide and multiply. Instead, the more T cells that are produced in the blood as the parent cells containing sjTRECs divide and produce daughter cells, the more the sjTRECs in those original T cells get "diluted" within the growing army of these immune cells. This proves that high levels of sjTREC in blood means that a large number of stem cells have been converted to parent T cells--each of which targets a specific foreign substance, according to Rupert Handgretinger, M.D., Ph.D., director of Stem Cell Transplantation at St. Jude and co-director of the Transplantation and Gene Therapy Program.

"sjTRECs appear only after the gene shuffling has successfully occurred in the parent cell," Handgretinger said. "So if we extract large numbers of sjTRECs from T cells in the blood of a patient about to undergo a stem cell transplant, that’s a good sign. It means the patient’s thymus is a good T-cell factory."

Handgretinger is the senior author of the Blood report.

The St. Jude team tested levels of sjTREC in the blood of 77 healthy donors who provided stem cells to their siblings. The researchers also tested 244 samples from 26 of the recipients themselves. The recipients had been treated for either white cell cancers (e.g., acute lymphoblastic leukemia) or red cell diseases (e.g., sickle cell disease).

Because blood from the normal, healthy donors contained 1,200 to 155,000 sjTREC copies per milliliter of blood, the investigators chose 1,200 as the lowest end of the normal range for sjTRECs.

The team found that transplant recipients who had more than 1,200 copies of sjTREC in each milliliter of their blood before transplantation were more likely than patients with fewer copies to experience successful reconstitutions of their T cell populations. In patients with fewer than 1,200 copies per milliliter, the transplantation was likely either to fail or be significantly slow in reconstructing the T cell population.

"This is the first demonstration that high levels of sjTREC in a potential stem cell recipient can predict that their thymus will successfully reconstitute their T cell population using donated stem cells," said Xiaohua Chen, Ph.D., first author of the Blood article. "This kind of information should help physicians improve their ability to manage individual patients by predicting how they will respond to stem cell transplants."

Other authors of this study are Raymond Barfield, Ely Benaim, Wing Leung, James Knowles, Dawn Lawrence, Mario Otto, Sheila A. Shurtleff, Geoffrey A. M. Neale, Frederick G. Behm and Victoria Turner.

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org

More articles from Life Sciences:

nachricht The dense vessel network regulates formation of thrombocytes in the bone marrow
25.07.2017 | Rudolf-Virchow-Zentrum für Experimentelle Biomedizin der Universität Würzburg

nachricht Fungi that evolved to eat wood offer new biomass conversion tool
25.07.2017 | University of Massachusetts at Amherst

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA mission surfs through waves in space to understand space weather

25.07.2017 | Physics and Astronomy

Strength of tectonic plates may explain shape of the Tibetan Plateau, study finds

25.07.2017 | Earth Sciences

The dense vessel network regulates formation of thrombocytes in the bone marrow

25.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>