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砷诱导一名难治性T细胞急性淋巴细胞白血病患者完全缓解,伴有独特的T细胞克隆演变但无分子学完全缓解:一例报告

Arsenic induced complete remission in a refractory T-ALL patient with a distinct T-cell clonal evolution without molecular complete remission: A case report.

作者信息

Wu Suijing, Xu Ling, Huang Xin, Geng Suxia, Xu Yan, Chen Shaohua, Yang Lijian, Wu Xiuli, Weng Janyu, DU Xin, Li Yangqiu

机构信息

Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.

Institute of Hematology, Jinan University, Guangzhou, Guangdong 510632, P.R. China.

出版信息

Oncol Lett. 2016 Jun;11(6):4123-4130. doi: 10.3892/ol.2016.4529. Epub 2016 May 5.

DOI:10.3892/ol.2016.4529
PMID:27313752
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4888266/
Abstract

Currently, arsenic trioxide therapy is widely used for the treatment of acute promyelocytic leukemia (APL), relapsed and refractory adult T-cell leukemia/lymphoma and myelodysplastic syndrome. Regarding the broad antitumor activity of arsenic, certain studies have been undertaken to test its efficacy in treating acute T-cell lymphoblastic leukemia (T-ALL) cell lines and patients; however, to the best of our knowledge, no reports document that arsenic is able to induce the remission of T-ALL patients. The present study reports the case of young male patient diagnosed with T-ALL, with no significant response to common chemotherapy regimens, who finally achieved complete remission without minimal residual disease (as detected by flow cytometry) due to arsenic treatment. This result is encouraging, and the present study has shown that malignant TCRαβ cell clones can be detected at the molecular level using reverse transcription-polymerase chain reaction (PCR) combined with the GeneScan technique. The result is mainly based on the T-cell receptor (TCR) Vβ1 clone (a 190-base pair PCR product that with the same complementarity determining region 3 length can be detected for all samples collected during various statuses) and on undetectable TCR Vγ subfamily members, at the time of disease diagnosis. It is important to analyze the dynamically changing TCR pool in leukemia patients during therapy. Although the molecular mechanism through which arsenic contributes to malignant clone elimination remains unclear in the case presented, the use of arsenic is expected to be effective for clinically treating refractory and relapsed T-ALL patients.

摘要

目前,三氧化二砷疗法广泛用于治疗急性早幼粒细胞白血病(APL)、复发难治性成人T细胞白血病/淋巴瘤和骨髓增生异常综合征。鉴于砷具有广泛的抗肿瘤活性,已开展了一些研究来测试其治疗急性T细胞淋巴细胞白血病(T-ALL)细胞系和患者的疗效;然而,据我们所知,尚无报告证明砷能够诱导T-ALL患者缓解。本研究报告了一例诊断为T-ALL的年轻男性患者,其对常规化疗方案无明显反应,最终因砷治疗实现了完全缓解且无微小残留病(通过流式细胞术检测)。这一结果令人鼓舞,并且本研究表明,使用逆转录-聚合酶链反应(PCR)结合基因扫描技术可在分子水平检测到恶性TCRαβ细胞克隆。结果主要基于疾病诊断时的T细胞受体(TCR)Vβ1克隆(一个190碱基对的PCR产物,对于在不同状态下收集的所有样本,均可检测到具有相同互补决定区3长度的该产物)以及未检测到的TCR Vγ亚家族成员。分析白血病患者治疗期间动态变化的TCR库很重要。尽管在所呈现的病例中,砷促进消除恶性克隆的分子机制仍不清楚,但预计使用砷对临床治疗难治性和复发性T-ALL患者有效。

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Arsenic trioxide induces oxidative stress, DNA damage, and mitochondrial pathway of apoptosis in human leukemia (HL-60) cells.三氧化二砷可诱导人白血病(HL-60)细胞产生氧化应激、DNA损伤及线粒体凋亡途径。
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