【摘要】 髓系白血病细胞“细胞动力学耐药”是指处于G₀期或增殖缓慢、细胞周期长于药物接触时间的白血病细胞对某些细胞周期特异性细胞毒药物产生耐药的现象。阿糖胞苷（Ara-C）为目前治疗急性髓系白血病（AML）标准诱导方案的药物之一。它是一种通过抑制DNA的合成,特异性地杀伤处于S期的白血病细胞的细胞周期特异性的细胞毒药物。³H-胸腺嘧啶核苷体内标记研究证实,在AML存在一部分处于增殖静止状态和增殖缓慢的白血病细胞。体外研究发现,某些造血生长因子（HGF）,如干细胞因子,IL-3,GM-CSF和G-CSF,在单用或联合应用条件下,不但能动员髓系白血病细胞进入细胞周期,使其对Ara-C的敏感性增加,细胞周期动力学耐药得以克服,而且对正常造血祖细胞有一定的保护作用。目前,有关HGF克服AML细胞动力学耐药临床研究结果表明,GM-CSF有可能提高患者的无病生存时间,副作用为血小板恢复延迟。显然,为明确HGF在克服AML细胞动力学耐药中的实际效果和可能的副作用,进一步进行HGF单独和联合条件下的大样本随机对照的前瞻性研究是十分必要的;另外,寻找能更有效的克服AML细胞周期耐药的HGF,也是应进一步研究的课题。更多还原

【Abstract】 Cytokinetic resistance of leukemic cells is a phenomenon that the blasts in quiescent state (G0) or with longer cell cycle transit time than the duration of exposure to chemotherapy may escape cytotoxicity of cell cycle specific cytotoxic agents. Cytarabine (Ara-C) is one of the cytotoxic drugs used most frequently in the treatment of acute myeloid leukemia (AML). Only the leukemic cells in S phase are sensitive to Ara-C that exerts its cytotoxic effect by inhibiting DNA synthesis. The existence of quiescent and slowly dividing leukemic cell population in AML has been demonstrated in vivo by using 3H-thymidine labeling techniques. Hematopoietic growth factors (HGFs) or cytokines, such as SCF, IL-3, GM-CSF and G-CSF, alone or in combination, can not only recruit the leukemic blasts into cycling state, rendering them more sensitive to the cytotoxicity of Ara-C, but also appear to protect normal residual hematopoi-etic progenitor population in vitro. The results of current available clinical trials on GM-CSF-priming and circumvention of cytokinetic resistance in AML seem to be of an advantage in disease-free survival. Delayed recovery of platelets is noted. However, before this approach can be routinely used as a standard regimen in combination with chemotherapy in the treatment of AML, more large, randomized, double-blinded, placebo controlled and prospective clinical trials are still needed to be done in order to confirm its benefits and side effects. In addition, to seek more priming-effective HGFs or their combinations and to apply them to clinical studies are other research directions in which we should undertake with great effort.更多还原