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Orphan nuclear receptors-induced ALT-associated PML bodies are targets for ALT inhibition

Date: 2024-05-24

Pediatric brain tumors and osteosarcomas often utilize the ALT (Alternative Lengthening of Telomeres) mechanism to length telomeres for cellular immortality. A research team led by Associate Research Fellow Dr. Liuh-yow Chen at the Institute of Molecular Biology, Academia Sinica, discovered that orphan nuclear receptors regulate telomere elongation through APBs (ALT-associated PML bodies) in ALT cancer cells. Additionally, they found that arsenic trioxide (As2O3), a treatment for acute promyelocytic leukemia, can target APBs and inhibit ALT activity in cultured ALT cancer cells and in mouse xenografts, which opens the possibility of repurposing As2O3 for ALT cancer treatments. This research provides deep insights into the biology of ALT-related cancers and a new potential avenue for their treatment. The study was published in Nucleic Acids Research on May 17, 2024. The first author of the paper is Venus Marie Gaela, a PhD student in TIGP-MCB at Academia Sinica. The research was funded by Academia Sinica and the National Science and Technology Council.