三磷酸腺苷生物荧光法在急性髓系白血病细胞体外药物敏感性检测的初步应用

中国药物警戒 ›› 2016, Vol. 13 ›› Issue (3): 132-137.

三磷酸腺苷生物荧光法在急性髓系白血病细胞体外药物敏感性检测的初步应用

王胤颖,刘聪艳,张维,贺景娟,苏力,孙婉玲

首都医科大学宣武医院血液科,北京100053

收稿日期:2016-02-15 修回日期:2016-04-12 出版日期:2016-03-20 发布日期:2016-04-12
通讯作者: 孙婉玲,女,副主任医师,副教授·硕导,血液系统疾病的基础与临床。E-mail:wanlingsun@live.cn
作者简介:王胤颖,女,在读硕士,血液系统疾病的基础与临床。
基金资助:
北京市卫生系统高层次卫生技术人才培养项目（2011-3-092）;首都医科大学基础临床合作研究基金（15JL07）;首都医科大学宣武医院英才培养计划。

Application of ATP Bioluminescence Assay in Chemosenstitivity of Acute Myeloid Leukemia Cells by ATP Bioluminescence in Vitro

WANG Yin-ying, LIU Cong-yan, ZHANG Wei, HE Jing-juan, SU Li, SUN Wan-ling

Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

Received:2016-02-15 Revised:2016-04-12 Online:2016-03-20 Published:2016-04-12

摘要/Abstract

摘要： 目的初步探索三磷酸腺苷生物荧光肿瘤体外药敏检测（ATP bioluminescence-tumor chemosensitivity assay, ATP-TCA）技术在急性髓系白血病（acute myeloid leukemia, AML）中的临床应用价值。方法采集18例初治AML患者的骨髓或外周血,分离单个核细胞,应用ATP-TCA技术,观察体外白血病细胞对化疗药物的敏感性,并分析体外药敏结果、危险度分层及临床疗效三者之间的关系。结果 18 例初治AML患者的白血病细胞在体外对8种化疗药物显示出不同的敏感性,有效率最高的是阿柔比星,无效率最高的是吡柔比星。在14例可进行疗效评价的初治 AML患者中观察到蒽环类药物体外敏感性与临床疗效之间的完全相符率为78.6%,不同危险度分层患者之间的临床疗效（P=0.012）和生存时间（P=0.018）均有显著差异,高危组患者生存时间最短。结论 AML体外药敏检测结果与临床治疗反应之间具有相关性趋势, ATP-TCA可能是开展AML个体化化疗的一种有效的体外药物筛选方法 ,尤其是老年AML。

关键词: 急性髓系白血病, 药敏检测, 三磷酸腺苷生物荧光法

Abstract: Objective To preliminarily explore the clinical value of ATP bioluminescence tumor chemosensitivity assay (ATP-TCA) in patients with acute myeloid leukemia (AML). Methods Peripheral blood or bone marrow mononuclear cells separated from newly diagnosed AML specimens were tested in vitro for cancer chemosensitivity to eight kinds of drugs by ATP-TCA, which was used for observing the susceptibility results in vitro and analyzing the relationships among the susceptibility results in vitro, risk stratification and clinical efficacy. Results Eighteen cases of AML patients displayed different sensitivities to these eight kinds of drugs in vitro.Different drugs had different tumor growth inhibition ratio in vitro, of which the highest efficiency is aclarubicin and the highest inefficiency is pirarubicin. Fourteen cases of de novo AML patients were evaluable for clinical efficacy. Entirely consistent rate between the susceptibility in vitro and clinical efficacy was 78.6%, according to the susceptibility results of anthracycline in chemotherapy regimens. Clinical efficacy (P=0.012) and survival time (P=0.018) in patients with three different groups of risk stratification were statistically significant. Patients in high-risk groups had the shortest lifetime. Conclusion The results of ATP-TCA assay were correlated well with clinical treatment responses. The assay may be an important and effective method for individual-based chemotherapy of AML, especially in elderly AML.

Key words: acute myeloid leukemia, drug screening assay, ATP bioluminescence assay

中图分类号:

R969
R979.1

王胤颖,刘聪艳,张维,贺景娟,苏力,孙婉玲. 三磷酸腺苷生物荧光法在急性髓系白血病细胞体外药物敏感性检测的初步应用[J]. 中国药物警戒, 2016, 13(3): 132-137.

WANG Yin-ying, LIU Cong-yan, ZHANG Wei, HE Jing-juan, SU Li, SUN Wan-ling. Application of ATP Bioluminescence Assay in Chemosenstitivity of Acute Myeloid Leukemia Cells by ATP Bioluminescence in Vitro[J]. Chinese Journal of Pharmacovigilance, 2016, 13(3): 132-137.

参考文献

[1] Glaysher S, Cree I A. Cell sensitivity assays: the ATP-based tumor chemosensitivity assay[J]. Methods MolBiol, 2011, 731: 247-257.
[2] Zhang J, Li H. Heterogeneity of tumor chemosensitivity in ovarian epithelial cancer revealed using the adenosine triphosphate-tumor chemosensitivity assay[J]. OncolLett, 2015, 9(5): 2374-2380.
[3] Fehm T, Zwirner M, Wallwiener D, et al. Antitumor activity of zoledronic acid in primary breast cancer cells determined by the ATP tumor chemosensitivity assay[J]. BMC Cancer, 2012, 12(1): 308.
[4] Vardiman J W, Thiele J, Arber D A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes[J]. Blood,
2009,114(5): 937-951.
[5] NCCN. NCCN Clinical Practice guidelines in Oncology: Acute Myeloid Leukemia, Version 1[EB/OL]. (2014-03-12) [ 2016-02- 01]. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp
[6] Cheson B D, Bennett J M, Kopecky K J, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards
for Therapeutic Trials in Acute Myeloid Leukemia[J]. J Clin Oncol. 2003. 21(24): 4642-4649.
[7] 中华医学会血液学分会白血病学组. 急性髓系白血病治疗的专家共识(第一部分)[J]. 中华血液学杂志, 2009, 30(6):429-431.
[8] 中华医学会血液学分会白血病学组. 急性髓系白血病治疗的专家共识(第二部分)[J]. 中华血液学杂志, 2010, 31(1):69-70.
[9] 孙黎明, 李苗, 杜淑旭，等. 细胞体外药敏试验与急性淋巴细胞白血病患儿临床治疗及预后的研究[J].实用儿科临床杂
志, 2011,26(3):174-176.
[10] Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays[J]. J Immunol Methods,1983, 65(1-2): 55-63.
[11] Mollgard L , Tidefelt U, Sundman-Engberg B, et al. In vitro chemosensitivity testing in acute non lymphocytic leukemia using the bioluminescence ATP assay[J].Leuk Res, 2000, 24(5): 445-452.
[12] 杨磊, 宋诸臣, 徐小红, 等. 三磷酸腺苷生物荧光法体外药敏试验指导复发或难治性非霍奇金淋巴瘤化疗的临床研究[J]. 白血病?淋巴瘤，2011, 20(10):590-593.
[13] Krug U, Rolig C, Koschmieder A, et al. Complete remission and early death intensive chemotherapy in patient aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes[J]. Lancet, 2010, 376(9757): 2000-2008.
[14] Faderi S, Ravandi F, Huang X, et al. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients[J]. Cancer, 2012, 118(18): 4471-4477.