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CREBBP histone acetyltransferase domain mutations predict response to mTOR inhibition in relapsed/refractory follicular lymphoma

Year: 2024
Type: article
Abstract: Summary Despite the clinical and molecular heterogeneity of follicular lymphoma (FL), there remains a lack of biomarker‐directed therapeutic approaches in routine clinical practice, with the notable exception of the EZH2 inhibitor tazemetostat in EZH2‐mutant FL. Here we examined whether gene mutation status predicts response to clinical mTOR inhibitors (mTORi) in FL, by performing targeted mutational profiling of biopsies from 21 relapsed/refractory FL patients treated with mTORi everolimus or temsirolimus within clinical trials. We observed an enrichment of mutations within the catalytic histone acetyltransferase (HAT) domain of CREBBP in mTORi‐responders, and describe distinct transcriptional characteristics and co‐occurring mutations of FL harbouring these mutations; reinforcing the growing appreciation of CREBBPHAT mutation as a key biological determinant and its promise as a therapeutic biomarker in FL.
DOI: 10.1111/bjh.19671
Authors: Emil Arjun Kumar, Koorosh Korfi, Findlay Bewicke‐Copley, Karina Close, James Heward, Thomas Witzig, Michael Leukam, Stephen Ansell, Jessica Scott, Andrew Clear, Alejo Efeyan, Michael Green, Reiner Siebert, Barrie Peck, Maria Calaminici, Jun Wang, Sonali Smith, Anne Novak, Jude Fitzgibbon, Jessica Okosun
Institutions: Queen Mary University of London, Barts Cancer Institute, Mayo Clinic, University of Chicago, Spanish National Cancer Research Centre, The University of Texas MD Anderson Cancer Center, Christian-Albrechts-Universität zu Kiel, University Hospital Schleswig-Holstein
Language: English
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $4,940
OpenAlex ID: W4401928362
FWCI: 0.26
Cites: 15
Cited by: 1
Related to: 10