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糖皮质激素(GC)是治疗儿童急性淋巴细胞白血病的重要药物,GC治疗的敏感性与儿童急性淋巴细胞白血病的预后密切相关。该文就近期国外对GC耐药性机制的研究进展进行综述。GC应用后糖皮质激素受体(GR)的数量自动上调、GRαmRNA高水平表达及GRβ/GRα比值的显著降低以及细胞周期调控因子Rb-1的低磷酸化等与GC耐药性呈负相关;GR基因的一些突变与多态性等与GC耐药性呈正相关;GR的蛋白质表达水平、膜受体以及各种分子伴侣等与GC耐药无相关性;而谷胱甘肽和谷胱甘肽-S转移酶、bcl-2变阻器等与GC耐药性的关系目前尚不明了。
Glucocorticoid (GC) is an important drug for the treatment of acute lymphoblastic leukemia in children. The sensitivity of GC treatment is closely related to the prognosis of childhood acute lymphoblastic leukemia. This review summarizes recent progress in the research of GC resistance mechanisms in foreign countries. After GC application, the number of glucocorticoid receptor (GR) was up-regulated automatically. The high expression of GRαmRNA and the significant decrease of GRβ / GRα ratio and the low phosphorylation of cell cycle regulatory factor Rb-1 were negatively correlated with GC resistance. Some mutations and polymorphisms of GR gene were positively correlated with GC resistance; GR protein expression, membrane receptors and various molecular chaperones were not related to GC resistance; while glutathione and glutathione The relationship between peptide-S transferase, bcl-2 varistor, and GC resistance is not known.