急性淋巴细胞白血病糖皮质激素耐药的分子机制及其相关问题

糖皮质激素(GC)能特异性地诱导淋巴细胞周期停滞和凋亡,因此几十年来一直是治疗淋巴系统肿瘤,尤其是急性淋巴细胞白血病(ALL)的主要组成药物。然而对GC产生耐药性是临床ALL治疗中常见的难题,也是导致治疗失败的主要原因。GC耐药的确切的分子机制尚未阐明,与不同的疾病类型、治疗方案,尤其是患者的遗传背景有关。最近发现mTOR激酶介导的信号通路的活化能够诱导淋巴细胞对GC耐药,以及mTOR激酶抑制剂雷帕霉素能够有效地逆转ALL细胞对GC耐药作用提示联合应用mTOR激酶抑制剂和GC有望成为治疗ALL的有效措施。GC敏感试验是儿童ALL的一项主要预后判断指标,然而本身还有很多局限性,因此有必要寻找精确的特异性高的体外GC敏感试验。

Glucocorticoid resistance in acute lymphoblastic leukemia: molecular mechanisms and related issues

Glucocorticoids(GC) can specifically induce cell cycle arrest and apoptosis in lymphoid cells,and therefore for decades constitute a central component in the treatment of lymphoid malignancies,particularly acute lym-phoblastic leukemia(ALL).However,the development of GC resistance is a serious clinical problem that complicates the ALL treatment and contributes to treatment failure.The molecular mechanisms of GC resistance are poorly understood and likely vary with disease type,treatment regimen,and particul...