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 Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>