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oai:ir.kagoshima-u.ac.jp:00016131 2026-03-03T15:02:18Z 57:86

Changes in intracellular activation-related gene expression and induction of Akt contribute to acquired resistance towards nelarabine in CCRF-CEM cell line CCRF-CEM細胞株における細胞内活性化関連遺伝子発現の変化とAktの誘導がネララビンに対する獲得抵抗性に寄与している Rindiarti, Almitra リンディアルティ, アルミトラ open access T-cell acute lymphoblastic leukemia drug resistance nelarabine combination therapy PI3K/Akt pathway 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨 Drug resistance is a major problem in treatment with nelarabine, and its resolution requires elucidation of the underlying mechanisms. We established two nelarabine-resistant subclones of the human T-cell lymphoblastic leukemia cell line CCRF-CEM. The resistant subclones showed changes in the expression of several genes related to nelarabine intracellular activation and inhibition of apoptosis. Activation of the Akt protein upon nelarabine treatment was observed in both subclones. The combination treatment with nelarabine and PI3K/Akt inhibitors was shown to inhibit cell growth. Cross-resistance was observed with ara-C and not with vincristine, daunorubicin, or etoposide treatment. Thus, changes in the expression of cellular activation-related genes, inhibition of apoptosis, and induction of Akt may be involved in the development of nelarabine resistance in the CCRF-CEM cell model. The use of different classes of chemotherapeutic agents and combination therapy with PI3K/Akt pathway inhibitors may be used to overcome resistance to nelarabine. Almitra Rindiarti, Yasuhiro Okamoto, Shunsuke Nakagawa, Junko Hirose, Yuichi Kodama, Takuro Nishikawa, Yoshifumi Kawano Changes in intracellular activation-related gene expression and induction of Akt contribute to acquired resistance toward nelarabine in CCRF-CEM cell line Leukemia & Lymphoma v.63(2) P.404-415 (2022) This is an Accepted Manuscript of an article published by Taylor & Francis in Leukemia & Lymphoma on 26 Jan 2022, available at: https://doi.org/10.1080/10428194.2021.1992617 Taylor & Francis 鹿児島大学 eng doctoral thesis VoR http://hdl.handle.net/10232/00032017 https://ir.kagoshima-u.ac.jp/records/16131 甲総研第659号 博士(医学) Doctor of Philosophy in Medical Science 2022-05-30 17701 鹿児島大学 https://ir.kagoshima-u.ac.jp/record/16131/files/Diss_アルミトラ_リンディアルティ_ISK659_2022.pdf application/pdf 3.6 MB 2023-01-27 2022-05-17 https://ir.kagoshima-u.ac.jp/record/16131/files/Abstract_アルミトラ_リンディアルティ_4516800249_2022.pdf application/pdf 359.5 kB 2022-06-14 2022-05-17 https://ir.kagoshima-u.ac.jp/record/16131/files/Result_Almitra_Rindiarti_isk_659.pdf application/pdf 115.1 kB 2022-06-13 2022-05-17 https://ir.kagoshima-u.ac.jp/record/16131/files/Comments_Almitra_Rindiarti_isk_659 .pdf application/pdf 52.3 kB 2022-06-13 2022-05-17