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

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