Cancer cells often express differentiation programs unrelated to their tissue of origin, although the contribution of these aberrant phenotypes tomalignancy is poorly understood. An aggressive subgroup of medulloblastomas (MBs) express a photoreceptor differentiation program normallyexpressed in the retina. The authors established that two photoreceptor-specific transcription factors, neural retina leucine zipper (NRL) and conerodhomeobox (CRX) genes, are master regulators of this program and are required for tumor maintenance in this subgroup. Beyondphotoreceptor lineage genes, they identified B-cell lymphoma-extra large (BCL-XL) protein (encoded by the BCL2-like 1 gene and atransmembrane molecule in the mitochondria) as a key transcriptional target of NRL. This provides evidence substantiating anti-BCL therapy as arational treatment opportunity for select MB patients. Their results highlight the utility of studying aberrant differentiation programs in cancer andtheir potential as selective therapeutic vulnerabilities.
展开▼
