Navigation Links
Circles Of DNA Might Help Predict Success Of Stem Cell Transplantation

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., s ickle 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.

###

This work was supported in part by the Assisi Foundation of Memphis and ALSAC.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tennessee, St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit http://www.stjude.org.


'"/>

Source:St. Jude Children鈥檚 Research Hospital


Related biology news :

1. Protein That Promotes Survival Of Stem Cells Might Be Key To Poor Leukemia Prognosis
2. Gene Signatures Predict Interferon Response For Multiple Sclerosis Patients
3. Chromosome Deletion Predicts Aggressive Neuroblastoma
4. Measuring Enzymes At End Of Cancer Pathway Predicts Outcome Of Tarceva, Taxol
5. Analysis Of Human Genome To Predict The Development Of Illnesses
6. Computational Tool Predicts How Drugs Work In Cells, Advancing Efforts To Design Better Medicines
7. Predicting success
8. Predicting chemotherapy outcome
9. Predicting successful outcomes in living-donor liver transplants
10. World-first Living Donor Islet Cell Transplant A Success; Procedure Offers Promise For Diabetics
11. Successful Test Of Single Molecule Switch Opens The Door To Biomolecular Electronics
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/11/2017)... 2017 No two people are believed ... New York University Tandon School of Engineering and ... that partial similarities between prints are common enough ... phones and other electronic devices can be more ... lies in the fact that fingerprint-based authentication systems ...
(Date:4/5/2017)... April 4, 2017 KEY FINDINGS ... expand at a CAGR of 25.76% during the forecast ... the primary factor for the growth of the stem ... https://www.reportbuyer.com/product/4807905/ MARKET INSIGHTS The global stem cell ... application, and geography. The stem cell market of the ...
(Date:3/30/2017)... 2017 Trends, opportunities and forecast in this ... technology (fingerprint, AFIS, iris recognition, facial recognition, hand geometry, ... end use industry (government and law enforcement, commercial and ... and others), and by region ( North America ... Asia Pacific , and the Rest of the ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... October 11, 2017 , ... Personal eye wash is a basic first aid supply for any ... So which eye do you rinse first if a dangerous substance enters both eyes? It’s ... Wash with its unique dual eye piece. , “Whether its dirt and debris, or ...
(Date:10/11/2017)... HILLS, Calif. , Oct. 11, 2017  SkylineDx today ... (ICR) and University of Leeds ... risk-stratify patients with multiple myeloma (MM), in a multi-centric Phase ... University of Leeds is the sponsor ... and ICR will perform the testing services to include high-risk ...
(Date:10/10/2017)... ... October 10, 2017 , ... San Diego-based team building and cooking events company, ... today. The bold new look is part of a transformation to increase awareness, ... significant growth period. , It will also expand its service offering from its signature ...
(Date:10/10/2017)... , Oct. 10, 2017 International research firm Parks Associates ... will speak at the TMA 2017 Annual Meeting , October 11 ... in the residential home security market and how smart safety and security ... Parks Associates: ... "The residential security ...
Breaking Biology Technology: