Gene expression ratio as a predictive determinant of nelarabine chemosensitivity in T-lymphoblastic leukemia/lymphoma.
Gene expression ratio as a predictive determinant of nelarabine chemosensitivity in T-lymphoblastic leukemia/lymphoma.
复制标题
基因表达比作为 T 淋巴细胞白血病/淋巴瘤奈拉滨化疗敏感性的预测决定因素。
DOI：
10.1002/pbc.26214
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Kawano Y.
中科院分区：
文献类型：
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作者：
Sripornsawan P;Okamoto Y;Nishikawa T;Kodama Y;Yamaki Y;Kurauchi K;Tanabe T;Nakagawa S;Shinkoda Y;Imuta N;Kawano Y.
背景奈拉滨已被用于治疗T细胞恶性肿瘤，包括T急性淋巴细胞白血病(T-ALL)/T淋巴母细胞淋巴瘤。然而，奈拉滨易感或耐药的机制尚未完全阐明。本研究的目的是确定纳拉滨转运和代谢在纳拉滨细胞毒性背景下的意义。结果患者ENT1、DCK、CDA、NT5C2、RRM1和RRM2基因的表达存在个体间的差异性，与Ara-G的LC_(50)无关，而(ENT1×DCK)/(CD_(A)×RRM1)的表达与LC_(50)显著相关(r=-0.831，P=0.0405)。结论患者对Nelabine的化疗敏感性受4种基因的平衡表达影响，其表达比例预测了T细胞对那拉滨的反应。
BackgroundNelarabine has been used for the treatment of T‐cell malignancies including T‐acute lymphoblastic leukemia (T‐ALL)/T‐lymphoblastic lymphoma. However, the mechanisms that underlie the susceptibility or resistance to nelarabine have not been fully elucidated. The aim of this study was to determine the significance of nelarabine transport and metabolism in the context of nelarabine cytotoxicity.ProcedureThe expression profiles of six genes in the nelarabine pathway were analyzed in blast cells from six patients with T‐ALL as well as in three T‐ALL cell lines. In vitro cytotoxicity (LC50of 9‐β‐d‐arabinofuranosylguanine [ara‐G]) was evaluated.ResultsThe mRNA expression ofENT1, DCK, CDA, NT5C2, RRM1, andRRM2in patients showed inter‐individual variability and was not correlated with the LC50of ara‐G. However, the ratio of (ENT1×DCK)/(CDA ×RRM1) expression was significantly correlated with LC50(r = –0.831,P= 0.0405).ConclusionsChemosensitivity to nelarabine is influenced by the balance of the expression of these four genes, and the ratio of their expression predicts the response of T‐cell malignancies to nelarabine.