Navigation Links
New mutations in leukemia: Researchers found mechanism that can help design future therapies

An international team of researchers has found a group of mutations involved in T-cell acute lymphoblastic leukemia (T-ALL), and showed that certain drugs, already in clinical use to treat other diseases, can eliminate the cells carrying these mutations.

Results* will be published next week in Nature Genetics and may promote the development of novel therapeutic approaches against leukemia.

The study was led by researcher Joo T. Barata at Instituto de Medicina Molecular in Lisbon, Portugal, jointly with J. Andres Yunes at Centro Infantil Boldrini in Campinas, So Paulo, Brazil, in collaboration with researchers from the National Cancer Institute in Frederick, Maryland, USA, the Erasmus Medical Center, Rotterdam, The Netherlands; and other laboratories in Europe and the US.

This is a basic research study with potential clinical impact, which was performed, in part, using samples from pediatric leukemia patients.

T-ALL affects mostly children. It is a blood cancer consisting in an uncontrolled growth in the number of T-lymphocytes (white blood cells from the immune system).

The onset of the disease can be triggered by different genetic mutations in genes involved in the proliferation and differentiation of T-cells.

The identification and study of mutations found in leukemia patients is particularly important to help develop more efficient and targeted therapies. Researchers now found a group of mutations that affect 9% of the patients with T-ALL and that may originate leukemia in these patients.

Most importantly, researchers demonstrated that a set of pharmaceutical drugs can eliminate the effect of these mutations, unraveling a potential therapeutic application for their discovery.

The current study shows that the mutations occur at the gene coding for a protein localized at the surface of T-cells, the interleukin-7 receptor (IL7R).

This protein contacts with both the exterior and the interior of the cells, acting as a bridge to transfer chemical information from the outside to the inside of cells. Information transfer occurs upon the binding of a bloodstream protein (interleukin-7) to the receptor, which triggers a cascade of cellular reactions that are essential for the correct development and proliferation of T-cells.

In the new study, researchers also found that the mutations promote non-stop, uncontrolled T-cell proliferation, independently of extracellular triggers. This capacity to induce cells to grow relentlessly is associated with the ability to originate tumors.

To help fighting the tumors that contain IL7R mutations, the team of researchers studied pharmaceutical drugs known to act in several steps of the referred cascade of cellular reactions and found that these drugs - which are already being tested against other diseases such as rheumatoid arthritis can stop cell proliferation induced in mutated cells and promote the elimination of these cells.

Says Joo T. Barata: "We discovered that the interleukin-7 receptor, which is essential for proper T-cell development, may also have a "dark side", acting as a Mr. Hyde of sorts. In particular, we found that certain mutations in this gene are involved in pediatric T-cell acute lymphoblastic leukemia and characterized how they act. Our observations allowed us to identify potential therapeutic weapons against these tumors. Although pediatric acute lymphoblastic leukemia is among the success stories in cancer therapy, improvements are still needed. We hope our findings will help further increase the efficacy and selectivity of already existing treatments."

Says J. Andrs Yunes, from Centro Infantil Boldrini in Campinas, So Paulo, Brazil: "Most mutations found resulted in the insertion of a cystein aminoacid into the IL7R. It is this new cystein that perverts the normal functioning of the receptor by linking two mutant IL7R molecules through disulfide bonds. I'm eager to know what is the probability of having a cystein codon insertion, in this specific location of the gene, to address whether this is random or not."

Says Scott K. Durum, from the National Cancer Institute in Frederick, Maryland, USA: "On the one hand, the IL-7 receptor should have seemed a likely cause of cancer because it normally stimulates cells to grow, which is what cancer cells do. On the other hand this seemed unlikely because there are normally two chains involved in signaling. However these remarkable mutations in just one of the chains circumvent the need for the second chain. In addition to existing drugs that can target this pathway, we aim to develop new antibodies against IL-7 receptor to treat these patients. "

Contact: Marta Agostinho
Instituto de Medicina Molecular

Related biology news :

1. Mutations not inherited from parents cause more than half the cases of schizophrenia
2. Research discovers frequent mutations of chromatin remodeling genes in TCC of the bladder
3. As new data wave begins, a gene study in one disease discovers mutations in an unrelated disease
4. UT Southwestern research reveals that significantly more genetic mutations lead to colon cancer
5. Environs prompt advantageous gene mutations as plants grow; changes passed to progeny
6. Mutations can spur dangerous identity crisis in cells
7. Evolutionary kings of the hill use good, bad and ugly mutations to speed ahead of competition
8. Scientists develop method to determine order of mutations that lead to cancer
9. Women with BRCA mutations can take hormone-replacement therapy safely after ovary removal
10. UMMS researchers develop new technology to screen and analyze genetic mutations
11. Researchers link gene mutations to Ebsteins anomaly
Post Your Comments:
(Date:4/28/2016)... First quarter 2016:   , Revenues amounted to ... of 2015 The gross margin was 49% (27) ... operating margin was 40% (-13) Earnings per share rose ... was SEK 249.9 M (21.2) , Outlook   ... The operating margin for 2016 is estimated to exceed ...
(Date:4/15/2016)... CHICAGO , April 15, 2016  A ... companies make more accurate underwriting decisions in a ... offering timely, competitively priced and high-value life insurance ... health screenings. With Force Diagnostics, rapid ... and lifestyle data readings (blood pressure, weight, pulse, ...
(Date:3/31/2016)... Florida , March 31, 2016 ... ) ("LegacyXChange" or the "Company") LegacyXChange ... potential users of its soon to be launched online ... ( ) will also provide potential ... use of DNA technology to an industry that is ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 2016   Boston Biomedical , an industry ... to target cancer stemness pathways, announced that its ... Drug Designation from the U.S. Food and Drug ... including gastroesophageal junction (GEJ) cancer. Napabucasin is an ... cancer stemness pathways by targeting STAT3, and is ...
(Date:6/23/2016)... ... June 23, 2016 , ... Charm Sciences, ... microbial test has received AOAC Research Institute approval 061601. , “This is another ... year,” stated Bob Salter, Vice President of Regulatory and Industrial Affairs. “The Peel ...
(Date:6/23/2016)... , ... June 23, 2016 , ... ... announced the launch of the Supplyframe Design Lab . Located in Pasadena, ... explore the future of how hardware projects are designed, built and brought to ...
(Date:6/23/2016)... BEACH, Calif. , June 23, 2016  Blueprint ... new biological discoveries to the medical community, has closed ... co-founder Matthew Nunez . "We have ... us with the capital we need to meet our ... will essentially provide us the runway to complete validation ...
Breaking Biology Technology: