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Telomerase inhibitor imetelstat kills AML cells via lipid ROS and ferroptosis

Nature Cancer volume 5, pages 12–13 (2024)Cite this article

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Imetelstat is a first-in-class telomerase inhibitor with efficacy in a number of blood cancers. Intriguingly, telomere lengths do not predict patient responses to imetelstat. We now show that imetelstat causes cell death by a mechanism that involves two regulators of fatty acid metabolism (FADS2 and ACSL4), driving excessive lipid reactive oxygen species formation and ferroptosis.

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Fig. 1: Genome-wide CRISPR–Cas9 editing to identify the key mediators of imetelstat efficacy.

References

  1. Tefferi, A. et al. A pilot study of the telomerase inhibitor imetelstat for myelofibrosis. N. Engl. J. Med. 373, 908–919 (2015). This paper reports clinical efficacy of imetelstat in patients with myelofibrosis.

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This is a summary of: Bruedigam, C. et al. Imetelstat-mediated alterations in fatty acid metabolism to induce ferroptosis as therapeutic strategy for acute myeloid leukemia. Nat. Cancer https://doi.org/10.1038/s43018-023-00653-5 (2023).

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Telomerase inhibitor imetelstat kills AML cells via lipid ROS and ferroptosis. Nat Cancer 5, 12–13 (2024). https://doi.org/10.1038/s43018-023-00654-4

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