{"title":"RUNX1 的表达受超级增强子调控，是成人 T 细胞白血病/淋巴瘤的治疗靶点。","authors":"Yuji Kobayashi, Koji Ando, Yoshitaka Imaizumi, Hikaru Sakamoto, Hideaki Kitanosono, Masataka Taguchi, Hiroyuki Mishima, Akira Kinoshita, Shara Bekytbek, Maki Baba, Takeharu Kato, Makiko Horai, Hidehiro Itonaga, Shinya Sato, Koh-Ichiro Yoshiura, Yasushi Miyazaki","doi":"10.1080/10428194.2024.2393258","DOIUrl":null,"url":null,"abstract":"<p><p>Super-enhancers (SEs) play an important role in regulating tumor-specific gene expression. JQ1, a Bromodomain-containing protein 4 (BRD4) inhibitor, exerts antitumor effects by disrupting SE-mediated regulation of gene expression. We investigated the anti-adult T-cell leukemia/lymphoma (ATL) effects of JQ1. JQ1 induced apoptosis and inhibited ATL cell proliferation. JQ1 suppressed <i>RUNX1</i>expression through the disruption of SE-mediated gene regulation. In the previous reports, it was shown that IC<sub>50</sub>s of AI-10-104 and Ro5-3335, RUNX1 inhibitors were 1-10 µM for lymphoblastic leukemia cell lines carrying <i>RUNX1</i> mutations. In the present study, we demonstrated that IC<sub>50</sub>s of AI-10-104 and Ro5-3335 were also 1-10 µM or lower for ATL cell lines. Simultaneously, AI-10-104 suppressed MYC proto-oncogene (c-MYC) expression. RUNX1 is a potential therapeutic target for ATL that promotes <i>c-MYC</i> expression. We showed that RUNX1 expression is regulated <i>via</i> SEs in ATL and that RUNX1 may be a novel therapeutic target for ATL.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"RUNX1 expression is regulated by a super-enhancer and is a therapeutic target in adult T-cell leukemia/lymphoma.\",\"authors\":\"Yuji Kobayashi, Koji Ando, Yoshitaka Imaizumi, Hikaru Sakamoto, Hideaki Kitanosono, Masataka Taguchi, Hiroyuki Mishima, Akira Kinoshita, Shara Bekytbek, Maki Baba, Takeharu Kato, Makiko Horai, Hidehiro Itonaga, Shinya Sato, Koh-Ichiro Yoshiura, Yasushi Miyazaki\",\"doi\":\"10.1080/10428194.2024.2393258\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Super-enhancers (SEs) play an important role in regulating tumor-specific gene expression. JQ1, a Bromodomain-containing protein 4 (BRD4) inhibitor, exerts antitumor effects by disrupting SE-mediated regulation of gene expression. We investigated the anti-adult T-cell leukemia/lymphoma (ATL) effects of JQ1. JQ1 induced apoptosis and inhibited ATL cell proliferation. JQ1 suppressed <i>RUNX1</i>expression through the disruption of SE-mediated gene regulation. In the previous reports, it was shown that IC<sub>50</sub>s of AI-10-104 and Ro5-3335, RUNX1 inhibitors were 1-10 µM for lymphoblastic leukemia cell lines carrying <i>RUNX1</i> mutations. In the present study, we demonstrated that IC<sub>50</sub>s of AI-10-104 and Ro5-3335 were also 1-10 µM or lower for ATL cell lines. Simultaneously, AI-10-104 suppressed MYC proto-oncogene (c-MYC) expression. RUNX1 is a potential therapeutic target for ATL that promotes <i>c-MYC</i> expression. We showed that RUNX1 expression is regulated <i>via</i> SEs in ATL and that RUNX1 may be a novel therapeutic target for ATL.</p>\",\"PeriodicalId\":18047,\"journal\":{\"name\":\"Leukemia & Lymphoma\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Leukemia & Lymphoma\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/10428194.2024.2393258\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Leukemia & Lymphoma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10428194.2024.2393258","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
RUNX1 expression is regulated by a super-enhancer and is a therapeutic target in adult T-cell leukemia/lymphoma.
Super-enhancers (SEs) play an important role in regulating tumor-specific gene expression. JQ1, a Bromodomain-containing protein 4 (BRD4) inhibitor, exerts antitumor effects by disrupting SE-mediated regulation of gene expression. We investigated the anti-adult T-cell leukemia/lymphoma (ATL) effects of JQ1. JQ1 induced apoptosis and inhibited ATL cell proliferation. JQ1 suppressed RUNX1expression through the disruption of SE-mediated gene regulation. In the previous reports, it was shown that IC50s of AI-10-104 and Ro5-3335, RUNX1 inhibitors were 1-10 µM for lymphoblastic leukemia cell lines carrying RUNX1 mutations. In the present study, we demonstrated that IC50s of AI-10-104 and Ro5-3335 were also 1-10 µM or lower for ATL cell lines. Simultaneously, AI-10-104 suppressed MYC proto-oncogene (c-MYC) expression. RUNX1 is a potential therapeutic target for ATL that promotes c-MYC expression. We showed that RUNX1 expression is regulated via SEs in ATL and that RUNX1 may be a novel therapeutic target for ATL.
期刊介绍：
Leukemia & Lymphoma in its fourth decade continues to provide an international forum for publication of high quality clinical, translational, and basic science research, and original observations relating to all aspects of hematological malignancies. The scope ranges from clinical and clinico-pathological investigations to fundamental research in disease biology, mechanisms of action of novel agents, development of combination chemotherapy, pharmacology and pharmacogenomics as well as ethics and epidemiology. Submissions of unique clinical observations or confirmatory studies are considered and published as Letters to the Editor
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
