Analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.
Analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.
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DOI：
10.1371/journal.pone.0258140
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Abdel-Azim H
中科院分区：
文献类型：
--
作者：
Luong A;Cerignoli F;Abassi Y;Heisterkamp N;Abdel-Azim H
骨髓是常规细胞毒性药物治疗人类b细胞前体急性淋巴细胞白血病（BCP-ALL）后原发性复发的常见部位。由于基质细胞在促进化疗耐药中起着重要作用，因此应该将基质细胞纳入体外药物治疗模型中。在这里，我们验证了xCELLigence系统作为连续共培养的新应用，以评估药物治疗对BCP-ALL细胞的长期影响。我们发现骨髓OP9基质细胞粘附在电极上，但随着患者来源的BCP-ALL细胞的分裂而逐渐移位，导致阻抗随着时间的推移而降低。药物治疗导致的BCP-ALL细胞死亡导致基质细胞重新粘附到电极上，增加阻抗。重要的是，长春新碱以剂量依赖的方式抑制敏感BCP-ALL细胞的增殖，并与阻抗增加相关。该系统能够区分两种复发费城染色体（Ph）阳性all对四种不同靶向激酶抑制剂的敏感性。此外，两种crlf2驱动的bcp - all细胞系对ruxolitinib的敏感性也存在差异。这些结果表明，阻抗可以作为一种新的方法来监测原代BCP-ALL细胞在保护性微环境细胞存在下的药物治疗和敏感性。
The bone marrow is a frequent location of primary relapse after conventional cytotoxic drug treatment of human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Because stromal cells have a major role in promoting chemotherapy resistance, they should be included to more realistically model in vitro drug treatment. Here we validated a novel application of the xCELLigence system as a continuous co-culture to assess long-term effects of drug treatment on BCP-ALL cells. We found that bone marrow OP9 stromal cells adhere to the electrodes but are progressively displaced by dividing patient-derived BCP-ALL cells, resulting in reduction of impedance over time. Death of BCP-ALL cells due to drug treatment results in re-adherence of the stromal cells to the electrodes, increasing impedance. Importantly, vincristine inhibited proliferation of sensitive BCP-ALL cells in a dose-dependent manner, correlating with increased impedance. This system was able to discriminate sensitivity of two relapsed Philadelphia chromosome (Ph) positive ALLs to four different targeted kinase inhibitors. Moreover, differences in sensitivity of two CRLF2-drivenBCP-ALL cell lines to ruxolitinib were also seen. These results show that impedance can be used as a novel approach to monitor drug treatment and sensitivity of primary BCP-ALL cells in the presence of protective microenvironmental cells.
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影响因子：
3.7
作者：
Limame R;Wouters A;Pauwels B;Fransen E;Peeters M;Lardon F;De Wever O;Pauwels P
通讯作者：
Pauwels P
DOI：
10.1016/j.bbagen.2019.01.011
发表时间：
2019-04-01
影响因子：
3
作者：
Georgoulia, Panagiota S.;Todde, Guido;Friedman, Ran
通讯作者：
Friedman, Ran
影响因子：
64.5
作者：
HERMANS, A;HEISTERKAMP, N;GROSVELD, G
通讯作者：
GROSVELD, G
影响因子：
5.2
作者：
Ji, Junfeng;Vijayaragavan, Kausalia;Bhatia, Mickie
通讯作者：
Bhatia, Mickie
影响因子：
5.7
作者：
Fei F;Stoddart S;Groffen J;Heisterkamp N
通讯作者：
Heisterkamp N