Navigation Links
New mutations in leukemia: Researchers found mechanism that can help design future therapies
Date:9/4/2011

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
marta-elisa@fm.ul.pt
351-918-485-068
Instituto de Medicina Molecular
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:3/28/2017)... , March 28, 2017 The ... Hardware (Camera, Monitors, Servers, Storage Devices), Software (Video Analytics, ... Region - Global Forecast to 2022", published by MarketsandMarkets, ... 2016 and is projected to reach USD 75.64 Billion ... and 2022. The base year considered for the study ...
(Date:3/24/2017)... 24, 2017 The Controller General of Immigration from ... Abdulla Algeen have received the prestigious international IAIR Award for the ... Continue Reading ... ... Controller Abdulla Algeen (small picture on the right) have received the IAIR ...
(Date:3/23/2017)... The report "Gesture Recognition and Touchless Sensing Market by Technology (Touch-based ... to 2022", published by MarketsandMarkets, the market is expected to be worth USD ... 2022. Continue Reading ... ... ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... and LAGUNA HILLS, Calif. , Oct. ... Cancer Research, London (ICR) and University ... SKY92, SkylineDx,s prognostic tool to risk-stratify patients with multiple myeloma ... MUK nine . The University of Leeds ... partly funded by Myeloma UK, and ICR will perform the ...
(Date:10/10/2017)... ... 2017 , ... San Diego-based team building and cooking events company, Lajollacooks4u, has ... The bold new look is part of a transformation to increase awareness, appeal to ... period. , It will also expand its service offering from its signature gourmet cooking ...
(Date:10/10/2017)... 10, 2017 International research firm Parks Associates announced ... at the TMA 2017 Annual Meeting , October 11 in ... residential home security market and how smart safety and security products impact ... Parks Associates: Smart Home ... "The residential security market has ...
(Date:10/9/2017)... DIEGO , Oct. 9, 2017  BioTech ... biological mechanism by which its ProCell stem cell ... critical limb ischemia.  The Company, demonstrated that treatment ... amount of limbs saved as compared to standard ... the molecule HGF resulted in reduction of therapeutic ...
Breaking Biology Technology: