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サイトウ ミネキ
Mineki Saito
齊藤 峰輝 所属 川崎医科大学 医学部 基礎医学 微生物学 職種 教授 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Evaluation of ALKBH2 and ALKBH3 gene regulation in patients with adult T-cell leukemia/lymphoma. |
| 掲載誌名 | 正式名：Virology journal 略 称：Virol J ISSNコード：1743422X/1743422X |
| 掲載区分 | 国外 |
| 巻・号・頁 | 21(1),pp.316 |
| 著者・共著者 | Yuji Wada, Tadasuke Naito, Takuya Fukushima, Mineki Saito |
| 発行年月 | 2024/12/04 |
| 概要 | BACKGROUND:Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic virus that causes malignant adult T-cell leukemia/lymphoma (ATL). Patients infected with HTLV-1 are considered HTLV-1 carriers, and a small proportion of patients progress to life-threatening ATL after a long asymptomatic phase. No antiviral agent or preventive vaccine specific for HTLV-1 infection is established in current situation. For development of countermeasures to combat HTLV-1 infection and ATL, it is essential to expand our knowledge about their pathogenesis. Recently, AlkB homolog (ALKBH) family have been shown to participate in the oncogenesis of various cancer types.METHODS:To investigate the potential role of ALKBH family members in the pathogenesis of ATL, we analyzed their gene expression dynamics in HTLV-1-infected T-cell lines and peripheral blood mononuclear cell-derived clinical specimens obtained from asymptomatic HTLV-1 carriers and patients with acute-type ATL. Epigenetic analysis was performed to dissect the mechanisms of ALKBH3 gene regulation using cultivated cells and a public dataset.RESULTS:The mRNA expression levels of ALKBH2 and ALKBH3 were significantly or suggestively decreased in asymptomatic HTLV-1 carriers, but reverted in acute-type ATL patients, correlating with HTLV-1 basic leucine zipper factor gene expression. Intriguingly, the pre-mRNA expression of ALKBH2 and ALKBH3 was significantly suppressed in patients infected with HTLV-1, but not in healthy controls. Epigenetic analysis was performed to dissect the mechanisms of ALKBH3 gene regulation. In vitro analysis suggested a possible relationship between DNA methylation and ALKBH3 gene expression. Investigation of a public dataset revealed that specific CpG sites exhibited characteristically regulated methylation states in HTLV-1-infected T-cell subsets.CONCLUSION:We discovered dynamically regulated patterns of ALKBH2 and ALKBH3 gene expression in patients infected with HTLV-1, and specific CpG sites epigene |
| DOI | 10.1186/s12985-024-02590-w |
| PMID | 39633427 |