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
{"title":"CREBBP组蛋白乙酰转移酶结构域突变可预测复发/难治性滤泡性淋巴瘤患者对mTOR抑制剂的反应。","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","doi":"10.1111/bjh.19671","DOIUrl":null,"url":null,"abstract":"<p><p>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 CREBBP<sup>HAT</sup> mutation as a key biological determinant and its promise as a therapeutic biomarker in FL.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CREBBP histone acetyltransferase domain mutations predict response to mTOR inhibition in relapsed/refractory follicular lymphoma.\",\"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\",\"doi\":\"10.1111/bjh.19671\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 CREBBP<sup>HAT</sup> mutation as a key biological determinant and its promise as a therapeutic biomarker in FL.</p>\",\"PeriodicalId\":135,\"journal\":{\"name\":\"British Journal of Haematology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-08-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"British Journal of Haematology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/bjh.19671\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"British Journal of Haematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/bjh.19671","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
CREBBP histone acetyltransferase domain mutations predict response to mTOR inhibition in relapsed/refractory follicular lymphoma.
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.
期刊介绍:
The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.