Olsson-Strömberg Ulla, Aleskog Anna, Björnberg Anneli, Höglund Martin, Simonsson Bengt, Bengtsson Mats, Barbany Gisela, Larsson Rolf, Lindhagen Elin
Department of Hematology, University Hospital, Uppsala, Sweden.
Anticancer Drugs. 2006 Jul;17(6):631-9. doi: 10.1097/01.cad.0000217423.59831.db.
The aims of this study were to evaluate the feasibility of using the non-clonogenic fluorometric microculture cytotoxicity assay in drug sensitivity testing of tumor cells from patients with chronic myeloid leukemia. In nine samples (six chronic phase, three blast crisis), the drug sensitivities in tumor cells from blood versus from bone marrow and fresh tumor cells versus cryopreserved were compared. In 26 samples obtained in chronic phase (pretreatment), in six samples from patients in blast crisis and in the K 562 cell line, the activity of imatinib alone and in combination with cytarabine, vincristine, daunorubicin, interferon, arsenic trioxide and homoharringtonine was evaluated. All chronic myeloid leukemia chronic phase samples were sensitive to imatinib, with a mean IC50 at 10.3 mumol/l. The chronic myeloid leukemia samples from blast crisis (n=6) were significantly more sensitive to imatinib than the samples from chronic phase (n=26) (P<0.05), with an IC50 mean at 0.4 mumol/l. In blast crisis samples, significant positive interaction effects were observed between imatinib and all other tested drugs except for interferon. In chronic phase samples, interferon, daunorubicin and arsenic trioxide were the drugs with the highest frequency of positive interactions with imatinib (P<0.05). We conclude that the fluorometric microculture cytotoxicity assay may be a useful method for drug sensitivity testing in chronic myeloid leukemia patient samples from both chronic phase and blast crisis, and that testing primary tumor cells may have advantages over cell line studies. Imatinib shows a higher in vitro activity and more positive drug interactions in cells from blast crisis than chronic phase chronic myeloid leukemia patients. Combinations between imatinib and interferon, daunorubicin and arsenic trioxide may be interesting for future clinical trials in patients with chronic myeloid leukemia chronic phase.
本研究的目的是评估使用非克隆荧光微量培养细胞毒性试验对慢性髓性白血病患者肿瘤细胞进行药敏试验的可行性。在9个样本（6个慢性期、3个急变期）中，比较了血液中肿瘤细胞与骨髓中肿瘤细胞以及新鲜肿瘤细胞与冻存肿瘤细胞的药物敏感性。在26个慢性期（预处理）样本、6个急变期患者样本以及K 562细胞系中，评估了伊马替尼单独使用以及与阿糖胞苷、长春新碱、柔红霉素、干扰素、三氧化二砷和高三尖杉酯碱联合使用时的活性。所有慢性髓性白血病慢性期样本对伊马替尼敏感，平均IC50为10.3 μmol/L。急变期的慢性髓性白血病样本（n = 6）对伊马替尼的敏感性显著高于慢性期样本（n = 26）（P<0.05），平均IC50为0.4 μmol/L。在急变期样本中，除干扰素外，伊马替尼与所有其他受试药物之间均观察到显著的正向相互作用。在慢性期样本中，干扰素、柔红霉素和三氧化二砷与伊马替尼正向相互作用的频率最高（P<0.05）。我们得出结论，荧光微量培养细胞毒性试验可能是一种用于慢性髓性白血病慢性期和急变期患者样本药敏试验的有用方法，并且检测原发性肿瘤细胞可能比细胞系研究具有优势。与慢性期慢性髓性白血病患者的细胞相比，伊马替尼在急变期细胞中显示出更高的体外活性和更多的正向药物相互作用。伊马替尼与干扰素、柔红霉素和三氧化二砷的联合使用可能对慢性髓性白血病慢性期患者未来的临床试验具有意义。
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