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Forgione, Michelle O; McClure, Barbara J; Page, Elyse C; Yeung, David T; Eadie, Laura N; White, Deborah L
Oncology Reports, 05/2022, Volume: 47, Issue: 5Journal Article
The presence of a mutation is a predictor of poor outcome in leukaemia, and efficacious targeted therapies for these patients are lacking. The curaxin CBL0137 has demonstrated promising antitumour activities in multiple cancers such as glioblastoma, acting through p53 activation, NF‑κB inhibition and chromatin remodelling. In the present study, it was revealed using Annexin‑V/7‑AAD apoptosis assays that CBL0137 has efficacy across several human acute leukaemia cell lines with wild‑type , but sensitivity is reduced in ‑mutated subtypes. A heterozygous loss‑of‑function mutation in the human RS4;11 cell line was generated, and it was demonstrated that heterozygous loss‑of‑function is sufficient to cause a significant reduction in CBL0137 sensitivity. To the best of our knowledge, this is the first evidence to suggest a clinically significant role for functional p53 in the efficacy of CBL0137 in acute leukaemia. Future CBL0137 clinical trials should include mutation screening, to establish the clinical relevance of mutations in CBL0137 efficacy.
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