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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:64 |
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| Enthalten in: |
Journal of clinical and experimental hematopathology : JCEH - 64(2024), 1 vom: 28. März, Seite 1-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Okatani, Takeshi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.03.2024 Date Revised 29.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.3960/jslrt.23038 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Okatani, Takeshi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a NOTCH1 | |
| 650 | 4 | |a lymphoproliferative disorders arising in immune deficiency/dysregulation | |
| 650 | 4 | |a methotrexate-associated lymphoproliferative disorders | |
| 650 | 4 | |a other iatrogenic immunodeficiency-associated lymphoproliferative disorders | |
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| 700 | 1 | |a Nishimura, Midori Filiz |e verfasserin |4 aut | |
| 700 | 1 | |a Egusa, Yuria |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshida, Sayako |e verfasserin |4 aut | |
| 700 | 1 | |a Nishimura, Yoshito |e verfasserin |4 aut | |
| 700 | 1 | |a Nishikori, Asami |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshino, Tadashi |e verfasserin |4 aut | |
| 700 | 1 | |a Yamamoto, Hidetaka |e verfasserin |4 aut | |
| 700 | 1 | |a Sato, Yasuharu |e verfasserin |4 aut | |
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