{"title":"成人 T 细胞白血病/淋巴瘤中 NOTCH1 和 FBXW7 改变的临床意义。","authors":"Yuma Sakamoto, Takashi Ishida, Ayako Masaki, Takayuki Murase, Eiichi Ohtsuka, Morishige Takeshita, Reiji Muto, Ilseung Choi, Hiromi Iwasaki, Asahi Ito, Shigeru Kusumoto, Nobuaki Nakano, Masahito Tokunaga, Kentaro Yonekura, Yukie Tashiro, Youko Suehiro, Shinsuke Iida, Atae Utsunomiya, Ryuzo Ueda, Hiroshi Inagaki","doi":"10.1007/s12185-024-03880-3","DOIUrl":null,"url":null,"abstract":"<p><p>Here, we investigated the clinical significance of NOTCH1 and FBXW7 alterations for adult T-cell leukemia/lymphoma (ATLL) treatment outcomes. NOTCH1 alterations were identified in 37 (14.4%) of 257 patients, of which 33 were single nucleotide variants/insertion-deletions in the PEST domain, and 7 were in the heterodimerization or LIN-12/Notch repeats domains. FBXW7 alterations were observed in nine ATLL patients (3.5%). For patients without allogeneic hematopoietic stem cell transplantation (HSCT), NOTCH1, but not FBXW7, alterations were significantly and independently associated with worse overall survival (median OS 0.5 years, 95% confidence interval [CI] 0.4-0.5 years for 27 patients with NOTCH1 alterations vs 1.8 years, 95% CI 1.3-2.2 years for 170 patients without). Also, for patients receiving mogamulizumab, but not allogeneic-HSCT, NOTCH1, but not FBXW7, alterations were significantly associated with worse survival (median survival from the first dose of mogamulizumab 0.4 years, 95% CI 0.3-0.5 years for 12 patients with NOTCH1 alterations vs 1.4 years, 95% CI 0.9-2.0 years for 87 without). In contrast, NOTCH1 alterations had no significant impact on survival of patients who did receive allogeneic-HSCT. Thus, mogamulizumab-containing treatment was unable to overcome treatment refractoriness of ATLL with NOTCH1 alterations. Therefore, patients with NOTCH1 alterations are recommended for allogeneic-HSCT.</p>","PeriodicalId":13992,"journal":{"name":"International Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":1.7000,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clinical significance of NOTCH1 and FBXW7 alterations in adult T-cell leukemia/lymphoma.\",\"authors\":\"Yuma Sakamoto, Takashi Ishida, Ayako Masaki, Takayuki Murase, Eiichi Ohtsuka, Morishige Takeshita, Reiji Muto, Ilseung Choi, Hiromi Iwasaki, Asahi Ito, Shigeru Kusumoto, Nobuaki Nakano, Masahito Tokunaga, Kentaro Yonekura, Yukie Tashiro, Youko Suehiro, Shinsuke Iida, Atae Utsunomiya, Ryuzo Ueda, Hiroshi Inagaki\",\"doi\":\"10.1007/s12185-024-03880-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Here, we investigated the clinical significance of NOTCH1 and FBXW7 alterations for adult T-cell leukemia/lymphoma (ATLL) treatment outcomes. NOTCH1 alterations were identified in 37 (14.4%) of 257 patients, of which 33 were single nucleotide variants/insertion-deletions in the PEST domain, and 7 were in the heterodimerization or LIN-12/Notch repeats domains. FBXW7 alterations were observed in nine ATLL patients (3.5%). For patients without allogeneic hematopoietic stem cell transplantation (HSCT), NOTCH1, but not FBXW7, alterations were significantly and independently associated with worse overall survival (median OS 0.5 years, 95% confidence interval [CI] 0.4-0.5 years for 27 patients with NOTCH1 alterations vs 1.8 years, 95% CI 1.3-2.2 years for 170 patients without). Also, for patients receiving mogamulizumab, but not allogeneic-HSCT, NOTCH1, but not FBXW7, alterations were significantly associated with worse survival (median survival from the first dose of mogamulizumab 0.4 years, 95% CI 0.3-0.5 years for 12 patients with NOTCH1 alterations vs 1.4 years, 95% CI 0.9-2.0 years for 87 without). In contrast, NOTCH1 alterations had no significant impact on survival of patients who did receive allogeneic-HSCT. Thus, mogamulizumab-containing treatment was unable to overcome treatment refractoriness of ATLL with NOTCH1 alterations. 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引用次数: 0
摘要
在此,我们研究了NOTCH1和FBXW7改变对成人T细胞白血病/淋巴瘤(ATLL)治疗结果的临床意义。在257例患者中,有37例(14.4%)发现了NOTCH1改变,其中33例是PEST结构域的单核苷酸变异/插入缺失,7例是异源二聚化或LIN-12/Notch重复序列结构域的单核苷酸变异/插入缺失。9名ATLLL患者(3.5%)出现了FBXW7变异。在未接受异基因造血干细胞移植(HSCT)的患者中,NOTCH1(而非FBXW7)的改变与较差的总生存期密切相关(27例NOTCH1改变患者的中位OS为0.5年,95%置信区间[CI]为0.4-0.5年;170例无NOTCH1改变患者的中位OS为1.8年,95%置信区间[CI]为1.3-2.2年)。此外,对于接受莫干珠单抗治疗而非异基因造血干细胞移植的患者,NOTCH1(而非 FBXW7)的改变与生存率的降低有显著相关性(12 例有 NOTCH1 改变的患者自首次使用莫干珠单抗起的中位生存期为 0.4 年,95% CI 为 0.3-0.5 年;87 例无 NOTCH1 改变的患者的中位生存期为 1.4 年,95% CI 为 0.9-2.0 年)。相比之下,NOTCH1改变对接受异基因造血干细胞移植的患者的生存期没有明显影响。因此,含莫干单抗的治疗无法克服伴有NOTCH1改变的ATLL的治疗难治性。因此,建议有NOTCH1改变的患者接受异基因造血干细胞移植。
Clinical significance of NOTCH1 and FBXW7 alterations in adult T-cell leukemia/lymphoma.
Here, we investigated the clinical significance of NOTCH1 and FBXW7 alterations for adult T-cell leukemia/lymphoma (ATLL) treatment outcomes. NOTCH1 alterations were identified in 37 (14.4%) of 257 patients, of which 33 were single nucleotide variants/insertion-deletions in the PEST domain, and 7 were in the heterodimerization or LIN-12/Notch repeats domains. FBXW7 alterations were observed in nine ATLL patients (3.5%). For patients without allogeneic hematopoietic stem cell transplantation (HSCT), NOTCH1, but not FBXW7, alterations were significantly and independently associated with worse overall survival (median OS 0.5 years, 95% confidence interval [CI] 0.4-0.5 years for 27 patients with NOTCH1 alterations vs 1.8 years, 95% CI 1.3-2.2 years for 170 patients without). Also, for patients receiving mogamulizumab, but not allogeneic-HSCT, NOTCH1, but not FBXW7, alterations were significantly associated with worse survival (median survival from the first dose of mogamulizumab 0.4 years, 95% CI 0.3-0.5 years for 12 patients with NOTCH1 alterations vs 1.4 years, 95% CI 0.9-2.0 years for 87 without). In contrast, NOTCH1 alterations had no significant impact on survival of patients who did receive allogeneic-HSCT. Thus, mogamulizumab-containing treatment was unable to overcome treatment refractoriness of ATLL with NOTCH1 alterations. Therefore, patients with NOTCH1 alterations are recommended for allogeneic-HSCT.
期刊介绍:
The International Journal of Hematology, the official journal of the Japanese Society of Hematology, has a long history of publishing leading research in hematology. The journal comprises articles that contribute to progress in research not only in basic hematology but also in clinical hematology, aiming to cover all aspects of this field, namely, erythrocytes, leukocytes and hematopoiesis, hemostasis, thrombosis and vascular biology, hematological malignancies, transplantation, and cell therapy. The expanded [Progress in Hematology] section integrates such relevant fields as the cell biology of stem cells and cancer cells, and clinical research in inflammation, cancer, and thrombosis. Reports on results of clinical trials are also included, thus contributing to the aim of fostering communication among researchers in the growing field of modern hematology. The journal provides the best of up-to-date information on modern hematology, presenting readers with high-impact, original work focusing on pivotal issues.