ID | 66572 |
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Author |
Okatani, Takeshi
Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Nishimura, Midori Filiz
Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
Egusa, Yuria
Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
Yoshida, Sayako
Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
Nishimura, Yoshito
Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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Nishikori, Asami
Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
Yoshino, Tadashi
Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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Yamamoto, Hidetaka
Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Sato, Yasuharu
Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
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Abstract | 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.
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Keywords | methotrexate-associated lymphoproliferative disorders
other iatrogenic immunodeficiency-associated lymphoproliferative disorders
lymphoproliferative disorders arising in immune deficiency/dysregulation
NOTCH1
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Published Date | 2024
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Publication Title |
Journal of Clinical and Experimental Hematopathology
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Volume | volume64
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Issue | issue1
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Publisher | Japanese Society for Lymphoreticular Tissue Research
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Start Page | 1
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End Page | 9
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ISSN | 1346-4280
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NCID | AA11556796
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2024 The Japanese Society for Lymphoreticular Tissue Research
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File Version | publisher
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PubMed ID | |
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Related Url | isVersionOf https://doi.org/10.3960/jslrt.23038
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License | https://creativecommons.org/licenses/by-nc-sa/4.0/
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