Navigation Links
Drug target identified for common childhood blood cancer
Date:7/31/2014

In what is believed to be the largest genetic analysis of what triggers and propels progression of tumor growth in a common childhood blood cancer, researchers at NYU Langone Medical Center report that they have identified a possible new drug target for treating the disease.

T-cell acute lymphoblastic leukemia is one of the most common and aggressive childhood blood cancers. An estimated quarter of the 500 adolescents and young adults diagnosed with the cancer each year in the U.S. fail to achieve remission with standard chemotherapy drugs.

In a cover-story report set to appear in the journal Cell online July 31, the NYU Langone team describes how they used advanced genetic scanning techniques to identify 6,023 so-called long, non-coding strands of RNA, vital chemical cousins of DNA, that were active in the immune system T cells taken from 15 boys and girls with T-cell acute lymphoblastic leukemia, but not active in the healthy T cells in three young people without the disease.

Further analysis found that chemically blocking the action of one of those non-protein-producing RNAs, known as leukemia-induced non-coding activator RNA-1, or LUNAR1 for short, stalled leukemia progression.

Study investigators say LUNAR1 was not singled out from RNA typically used by DNA to make proteins, but rather from among the most prevalent RNA long chemical strands of translated DNA, previously termed "junk DNA" which can help transcribe DNA but never fully assemble proteins. They say these long non-coding RNAs are increasingly recognized as key to regulating many cell functions.

Senior study investigator and NYU Langone cancer biologist Iannis Aifantis, PhD, says the study offers preliminary evidence that drugs blocking LUNAR1 could treat T-cell acute lymphoblastic leukemia and a long-sought alternative to chemotherapeutic drugs that kill both cancer and normal cells.

Aifantis, a professor and chair of pathology at the Laura and Isaac Perlmutter Cancer Center at NYU Langone, and an early career scientist at the Howard Hughes Medical Institute, also says LUNAR1 could aid in diagnosing the blood cancer.

"Our study shows that LUNAR1 is highly specific for T-cell acute lymphoblastic leukemia and plays a key role in how this cancer develops," he says, pointing out that overproduction of LUNAR1 was recorded in almost all (90 percent) of leukemia patients tested.

Moreover, Aifantis says, his team's latest findings suggest that development of future cancer therapies based on the underlying genetics of each patient should involve "not just mutations in someone's DNA, but also alterations in the makeup of RNA."

Among the study's other key findings was that while LUNAR1 does not produce cancerous proteins on its own, its production was essential to the cell-to-cell signaling action of another protein, insulin-like growth factor 1 receptor (IGF-1R), already tied to many cancers, including leukemia.

Further laboratory experiments showed that the gene coding for LUNAR1 is near the gene for IGF-1R and located toward the chromosomes' ends, known as telomeres. When activated, LUNAR1's position allows it to chemically loop back and, in turn, bind to and activate IGF-1R.

Researchers zeroed in on LUNAR1 by pinpointing those RNAs that also were active in the NOTCH1 biological pathway. They say the NOTCH1 pathway is common to many cancers, but is especially active in at least half of all people with T-cell acute lymphoblastic leukemia. LUNAR1 stood out right away, they say, as the most highly expressed long, non-coding RNA, of which more than half were newly discovered.

According to Aifantis, his team's research shows that T-cell acute lymphoblastic leukemia, as is the case in many other cancers, could be simply described as a condition of "too much errant signaling." He says in normal T cells, the long, non-coding RNAs such as LUNAR1 are not transcribed, NOTCH1 is inactive, and there is no looping back of LUNAR1 to activate IGF-1R.

To confirm their findings, researchers also transplanted human leukemia T cells into mice to prompt tumor growth, and chemically blocked LUNAR1 in some of the animals. Tumor growth stalled only in those mice whose LUNAR1 was inactivated.

Aifantis says his team's next steps are to develop more effective inhibitors of LUNAR1, preferably something that would precisely target any one or more of its 200-plus component nucleotides.


'/>"/>

Contact: David March
david.march@nyumc.org
212-404-3528
NYU Langone Medical Center / New York University School of Medicine
Source:Eurekalert

Related medicine news :

1. Targeted therapeutics for colon cancer to be presented at AACR meeting
2. First targeted nanomedicine to enter human clinical studies
3. SMART heart eases heart ache, targets cardiac patients emotional well-being
4. Target set on cancer gene MCL1
5. Scientists tailor cell surface targeting system to hit organelle ZIP codes
6. IBN discovers human neural stem cells with tumor targeting ability
7. A closer look at PARP-1 reveals potential new drug targets
8. Highly targeted irradiation as good as whole breast radiotherapy in early stage cancer
9. Breathing during radiotherapy - how to hit the treatment target without causing collateral damage
10. Scientists identify new target to battle rheumatoid arthritis
11. Scientists identify possible drug target for acute pancreatitis
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/6/2016)... ... 2016 , ... A wide variety of national pet product manufacturers, companies and brands will gather ... Wednesday, May 18 from noon to 8 p.m. at New York City’s Roger Smith Hotel. ... established home, garden, outdoor and safety pet products in today’s marketplace. , Petrend ...
(Date:5/6/2016)... ... May 06, 2016 , ... Logically, spring weather, with its moderate humidity ... is too cold, dry or hot, water on the eye surface can evaporate, creating ... the surrounding air. There’s only one problem, according to radio show and water advocate ...
(Date:5/6/2016)... ... , ... Canadian author Mark Black is a speaker, author, and life strategy coach ... world … with the help of his publisher Strategic Book Group and its subsidiary ... hospital bed waiting for a miracle: He needed a heart and double-lung transplant. From this ...
(Date:5/6/2016)... ... ... Overseer at The House of Yahweh, has written a new article this week meant to ... stop cancer. Yisrayl says there are too many suffering and dying from the disease to ... pay close attention and take action. The Pastor says that the root cause of all ...
(Date:5/6/2016)... , ... May 06, 2016 , ... ... and David Konur, CEO of Cardiovascular Institute of the South announced today that ... performing a live case of an Intravascular Ultrasound Guided Coronary Atherectomy. ...
Breaking Medicine News(10 mins):
(Date:5/5/2016)... Endo International plc (NASDAQ: ENDP ) (TSX: ENL) ... former president of Allergan, Inc. and current CEO of Chase ... of TPG Capital, to its Board of Directors. The appointments ... "Endo recently embarked on a search for new Board members ... Doug and Todd are experienced leaders, and we are extremely ...
(Date:5/5/2016)... Grand Cayman , May 5, 2016 Progra ... successful trial of Oxitec , s mosquito ... Aedes aegypti by 96 % ... (MRCU) announced a new plan to fight wild Aedes aegypti, the ... these diseases on the island of Grand Cayman .  MRCU, ...
(Date:5/5/2016)... May 5, 2016 Research and ... PET Imaging in the USA"  report to their offering.  ... information on the current Positron Emission Tomography (PET) scanner ... market. Along with the current known number ... USA , the report also contains a detailed ...
Breaking Medicine Technology: