{"title":"甲氨蝶呤相关淋巴组织增生性疾病中Notch1蛋白表达分析","authors":"Takeshi Okatani, Midori Filiz Nishimura, Yuria Egusa, Sayako Yoshida, Yoshito Nishimura, Asami Nishikori, Tadashi Yoshino, Hidetaka Yamamoto, Yasuharu Sato","doi":"10.3960/jslrt.23038","DOIUrl":null,"url":null,"abstract":"<p><p>Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary.</p>","PeriodicalId":45936,"journal":{"name":"Journal of Clinical and Experimental Hematopathology","volume":null,"pages":null},"PeriodicalIF":0.9000,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11079991/pdf/","citationCount":"0","resultStr":"{\"title\":\"Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders.\",\"authors\":\"Takeshi Okatani, Midori Filiz Nishimura, Yuria Egusa, Sayako Yoshida, Yoshito Nishimura, Asami Nishikori, Tadashi Yoshino, Hidetaka Yamamoto, Yasuharu Sato\",\"doi\":\"10.3960/jslrt.23038\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary.</p>\",\"PeriodicalId\":45936,\"journal\":{\"name\":\"Journal of Clinical and Experimental Hematopathology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.9000,\"publicationDate\":\"2024-03-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11079991/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical and Experimental Hematopathology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3960/jslrt.23038\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/28 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical and Experimental Hematopathology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3960/jslrt.23038","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/28 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
甲氨蝶呤(MTX)相关淋巴组织增生性疾病(MTX-LPD)是一种在接受MTX治疗的患者中出现的淋巴组织增生性疾病。其发病机制尚不明确,但被认为是多种因素的复杂相互作用,如潜在的自身免疫性疾病活动、MTX 的使用、Epstein-Barr 病毒感染和衰老。NOTCH 基因编码一种信号通路的受体,该信号通路调节各种基本的细胞过程,如胚胎发育过程中的增殖和分化。据报道,NOTCH1 基因突变见于 B 细胞肿瘤,包括慢性淋巴细胞白血病/淋巴瘤、套细胞淋巴瘤和弥漫大 B 细胞淋巴瘤(DLBCL)。最近还有报道称,移植后淋巴组织增生性疾病和血管免疫母细胞性T细胞淋巴瘤的CD20阳性细胞中也发现了NOTCH1突变,这可能与免疫缺陷的淋巴瘤发生有关。在本研究中,为了探讨NOTCH1与MTX-LPD发病机制的关系,我们对MTX-LPD病例[组织学上为DLBCL型(n = 24)和经典型霍奇金淋巴瘤(CHL)型(n = 24)]和新生淋巴瘤病例[DLBCL(n = 19)和CHL(n = 15)]的细胞核中Notch1的蛋白表达进行了免疫组化评估。结果显示,在MTX-LPD病例中,Notch1蛋白的表达在DLBCL型中明显高于CHL型(P<0.001)。此外,在DLBCL形态病例中,Notch1在MTX-LPD组的表达量往往高于新生组,但差异不显著(P = 0.0605)。结果表明,NOTCH1可能参与了MTX作用下B细胞的增殖和肿瘤发生。有必要开展进一步研究,包括基因研究。
Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders.
Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary.