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VJHemOnc Podcast
iwAL 2022 Session V: mechanisms of resistance to targeted therapies in AML
Dec 6, 2022
Naval Daver and Paresh Vyas discuss mechanisms of resistance to targeted therapies in AML, including the impact of small clones and non-cell intrinsic effects. They explore the modulation of leukemia by therapies and the potential of using companion diagnostics and immunotherapies to predict long-term responders. The podcast also highlights the importance of testing for flip three mutation in AML patients and the role of epigenetic targets in therapy resistance.
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Quick takeaways
- The phenomenon of low allelic burden mutations still responding to inhibitors targeting IDH1, IDH2, and FLT3 mutations suggests non-cell intrinsic effects of mutant leukemia and impacts on wild type signaling may be responsible for these responses.
- Early detection of FLT3 mutations in IDH patients during early stages of the disease can help tailor molecular targeted therapies, presenting opportunities for predicting long-term responders and relapses.
Deep dives
Resistance Mechanisms to Targeted Agents in Acute Myeloid Leukemia
The podcast episode delves into the discussion about the resistance mechanisms to novel targeted agents in acute myeloid leukemia (AML). The experts highlight the puzzling phenomenon of patients with low allelic burden mutations still responding to inhibitors targeting IDH1, IDH2, and FLT3 mutations. It is suggested that non-cell intrinsic effects of the mutant leukemia on other clones, as well as impacts on wild type signaling, may be responsible for these responses. The discussion also explores potential mechanisms such as the role of 2HG in IDH inhibitor response and the impact of wild type FLT3. Additionally, the role of MCL1 and immune modulation in AML treatment is discussed as an important avenue for further development.
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