Navigation Links
New culprit discovered in T-cell acute lymphoblastic leukemia
Date:1/12/2012

A new study published in the journal Nature Medicine by NYU Cancer Institute researchers, shows how the cancer causing gene Notch, in combination with a mutated Polycomb Repressive Complex 2 (PRC2) protein complex, work together to cause T- cell acute lymphoblastic leukemia (T-ALL).

T-ALL is an aggressive blood cancer, predominately diagnosed in children. It occurs when one lymphoblast, an immature white blood cell, turns malignant, multiplying uncontrollably and spreading rapidly throughout the body. If left untreated, the disease can be fatal in a few weeks. Cancer-causing Notch mutations in T-ALL are well established, yet the detailed molecular mechanism mediating this Notch-induced cancer cell transformation was unknown until now.

"Our study presents new insight into how Notch acts in an antagonistic mode with PRC2 to promote T-ALL," said senior author, Iannis Aifantis, PhD, associate professor in the Department of Pathology and a member of the NYU Cancer Institute, an NCI-designated cancer center at NYU Langone Medical Center. "Moreover, our study shows frequent genetic inactivation on the genetic loci encoding for PRC2 components, inhibits its normal role as a gene expression regulator and further proves the tumor suppressor role of the complex in this disease."

The study shows a new dynamic interplay between Notch and PRC2 function. In the study, researchers analyzed Notch-driven epigenetic gene expression regulation changes in T-ALL. Findings show a clear loss of PRC2 function from the sites of Notch1 binding. In addition, researchers found recurrent gene mutations and deletions of the components of PRC2 in T-ALL patient samples. In the study, loss of PRC2 function fueled the Notch mutation. This provides evidence for a central role of deregulation of PRC2 in Notch-induced T-ALL.

"The inactivation of PRC2 complex due to Notch in T-ALL constitutes an important pathogenetic event in the formation of this potentially deadly disease," said lead author of the study Panagiotis Ntziachristos, PhD, of the Department of Pathology at NYU Langone. "The PRC2 genetic alteration amplifies the Notch oncogene's communication signals leading to T-ALL. Our study experiments uncover a specific epigenetic switch during the progression of the disease that can be further exploited for the development of targeted epigenetic therapies."

The study shows T-ALL as an epigenetic disease, regulated by a subtle equilibrium between oncogenes and tumor suppressors. Oncogenes like Notch can infiltrate the normal function of PRC2 in specific gene loci leading to cancerous cell transformation. Mutations in PRC2 assist oncogenes like Notch by altering their DNA gene expression.

"Our studies offer new therapy avenues for the treatment of T-ALL," said Dr. Aifantis. "The detection of new genetic alterations in T-ALL provides a new platform for selecting potential treatment strategies for the disease. Drugs that can target histone demethylases, enzymes that catalyze the H3K27me3 modification, could be used alone or in combination with Notch1 inhibitors for the treatment of the disease."


'/>"/>

Contact: Lauren Woods
lauren.woods@nyumc.org
212-404-3555
NYU Langone Medical Center / New York University School of Medicine
Source:Eurekalert

Related medicine news :

1. Researchers discover new culprit in atherosclerosis
2. Extra Calories, Low Protein Are Culprits in Weight Gain
3. Expert Panel Pinpoints Environmental Culprits in Breast Cancer
4. New culprit found in Lou Gehrigs disease
5. Researchers search for culprit behind dry eyes, mouths and more
6. Key culprit identified in breast cancer metastasis
7. Lung cancer culprit could offer target for therapy, UT Southwestern researchers report
8. Researchers identify breast cancer culprits
9. Gene discovered for Weaver syndrome
10. Dual-acting class of antimalarial compounds discovered by Novartis with potential to prevent and treat malaria
11. A better way to count molecules discovered
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... June 27, 2016 , ... ... strategic partnership with Connance, a healthcare industry leader providing predictive analytics to ... technology combine to provide health systems, hospitals and ambulatory surgical centers with ...
(Date:6/27/2016)... ... 27, 2016 , ... TopConsumerReviews.com recently awarded their highest five-star rating to Best ... individuals in the United States and Canada wear eyeglasses. Once considered to be a ... and make a fashion statement. Even celebrities use glasses as a way of creating ...
(Date:6/26/2016)... Creek, Michigan (PRWEB) , ... June 26, 2016 , ... ... joined as sponsor of the 2016 Cereal Festival and World’s Longest Breakfast Table in ... in honor of the city’s history as home to some of the world’s leading ...
(Date:6/26/2016)... ... , ... PawPaws brand pet supplements owned by Whole Health Supply ... health of felines. The formula is all-natural and is made from Chinese herbs that ... Cat Kidney Support Supplement Soft Chews are Astragalus Root Extract and Rehmannia Root ...
(Date:6/26/2016)... Lake Orion, Clarkston, Michigan (PRWEB) , ... June ... ... direction with respect to fertility once they have been diagnosed with endometriosis. These ... tolerable intercourse but they also require a comprehensive approach that can help for ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016  Consumers have ... and regulators/payers have placed more emphasis on patient ... patient support programs in the pharmaceutical industry have ... medications. Consequently, pharmaceutical companies are focusing on becoming ... are providing products and services that improve health. ...
(Date:6/24/2016)... DUBLIN , June 24, 2016 ... addition of the "Structural Electronics 2015-2025: Applications, ... In-Mold Electronics, Smart ... Integrated Photovoltaics Structural electronics involves ... as load-bearing, protective structures, replacing dumb structures such ...
(Date:6/24/2016)... PUNE, India , June 24, 2016 ... "Pen Needles Market by Type (Standard Pen Needles, Safety ... 12mm), Therapy (Insulin, GLP-1, Growth Hormone), Mode of Purchase ... published by MarketsandMarkets, This report studies the market for ... is expected to reach USD 2.81 Billion by 2021 ...
Breaking Medicine Technology: