T-cell acute lymphoblastic leukemia (T-ALL) is an acute form of blood cancer primarily found in children that could turn fatal if left untreated. As a crucial clue in this terrain, scientists from the New York University Cancer Institute have demonstrated how a combination of Notch and mutated Polycomb Repressive Complex 2 (PRC2) protein leads to T-ALL.
The scientists found that the PRC2 protein is apparently deactivated by the Notch which paves the path to T-ALL. This protein complex seems to encounter genetic changes in the process that expands the cancer–causing gene Notch’s interactions, thereby causing the disease.
“Our study presents new insight into how Notch acts in an antagonistic mode with PRC2 to promote T-ALL. 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,” commented 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.
The scientists revealed that T-ALL is an epigenetic disease controlled by a restrained balance between oncogenes like Notch and tumor suppressors like PRC2. Oncogenes have the capacity to impede normal operations of PRC2 at a particular gene loci, thus leading to cancerous cell transformation.
This analysis offers hope for new treatment strategies where drugs targeting histone demethylases could be used along with Notch1 inhibitors for the treatment of T-ALL. The report is published in the journal, Nature Medicine.