Post by CeMM

🧬 𝗔 𝗻𝗲𝘄 𝗮𝗽𝗽𝗿𝗼𝗮𝗰𝗵 𝘁𝗼 𝗳𝗶𝗴𝗵𝘁 𝗰𝗵𝗶𝗹𝗱𝗵𝗼𝗼𝗱 𝗹𝗲𝘂𝗸𝗲𝗺𝗶𝗮: 𝗿𝗲𝗺𝗼𝘃𝗲 𝘁𝗵𝗲 𝘀𝗰𝗮𝗳𝗳𝗼𝗹𝗱, 𝗻𝗼𝘁 𝘁𝗵𝗲 𝗽𝗿𝗼𝘁𝗲𝗶𝗻 Acute myeloid leukemia (AML) is one of the most aggressive childhood blood cancers. While survival rates have improved, relapse remains a major challenge. Promising new approaches target leukemia cells’ molecular vulnerabilities, including therapies that disrupt genetic regulation. However, cancer cells often have redundant backup mechanisms. If one component fails, another steps in to ensure survival. Instead of directly targeting a cancer-driving protein, researchers from St. Anna Children's Cancer Research Institute (CCRI) and CeMM, in the group of CeMM Adjunct PI Davide Seruggia, took a different approach by removing the structural framework that keeps it stable. Published in 𝘕𝘢𝘵𝘶𝘳𝘦 𝘊𝘰𝘮𝘮𝘶𝘯𝘪𝘤𝘢𝘵𝘪𝘰𝘯𝘴, the study shows that disrupting the SAGA complex, a protein scaffold essential for the stability of the enzyme KAT2A (which is involved in gene activation and has long been considered a vulnerability of AML cells), triggers a domino effect. Without this support, KAT2A loses its function and is rapidly degraded by the cell’s quality-control system, thereby halting leukemia cell growth. This strategy overcomes a key challenge in AML. When KAT2A is directly inhibited, a related protein can compensate. By targeting the scaffold instead, this workaround is bypassed, revealing a previously hidden vulnerability. The findings highlight a promising new concept in cancer therapy: targeting protein stability and structure rather than the protein itself. 🔗 Read more: https://bit.ly/484XvFv 📄 Publication: https://bit.ly/4cPghT5 📷 From L to R: Senior author Davide Seruggia and first author Paul Batty (© St Anna CCRI). 📷 Fluorescence microscopy image of human HAP1 cells. DNA is shown in magenta, while cells expressing a green fluorescent marker indicate successful delivery of CRISPR guide RNAs for gene editing (© Seruggia Group, St Anna CCRI). #Leukemia #AML #ChildhoodCancer #CancerResearch