MDS去甲基化治疗__培训课件.ppt

Decitabine vs. Azacitidine Azacitidine和Decitabine均为胞嘧啶甲基化的有效抑制物。可与DNA结合，抑制DNMT（DNA甲基转移酶）的活性，随着细胞分裂次数的增加，DNA甲基化程度进行性的降低，使因高度甲基化而失活的基因表达上调。 * Decitabine vs. Azacitidine Decitabine 拥有更快的起效时间和更高的MDS克隆细胞清除率。 Decitabine可能拥有更高的CR 。 两者的比较研究还在进行中。 去甲基化药物无效 目前认为：一旦出现下述情况即认为属“去甲基化药物无效”，包括：缺乏CR、PR及血液学改善或直接进展至AML，尤其是外周血细胞计数的失调控（增殖）或阻止继续治疗的过度毒性。判断治疗失败之前的最小疗程数为4-6个。 小结 1 染色体分析对地西他滨治疗的选择有重要帮助，或地西他滨能够改善骨髓染色体核型。 2 地西他滨治疗后中性粒细胞减少引起的感染必须重视和积极预防。 3 国内或省内应该开展地西他滨治疗MDS长期生存研究。 * * * The myelodysplastic syndromes (MDS) are a group of conditions that are caused by the abnormal maturation of blood-forming cells in the bone marrow. As a result, the bone marrow cannot produce a sufficient number of mature blood cells, and those that are produced do not function normally. While the production of erythrocytes, granulocytes, monocytes, and platelets may all be affected in patients with MDS, they will usually have normal T and B lymphocytes. The underlying cause of MDS is a chromosomal abnormality that develops in a haematopoietic stem cell that changes it into a malignant cell. The abnormality may result from DNA damage that is caused by, for example, prior cancer therapy or exposure to environmental toxins. As this cell reproduces by mitotic division, it forms a clone of cells in which the abnormality persists. The damaged stem cell population produces progenitor blast cells that fail to respond to normal control signals and thus fail to differentiate into functional blood cells. * * * In MDS, the population of blast cells progressively replaces normal bone marrow cells. As a result, the number of blast cells in the bone marrow increases, while levels of mature, circulating cells decline (cytopenias). In addition, many mature cells that are released into the bloodstream have visible cellular abnormalities (i.e. dysplasias) and do not function normally. The defective cells produce cytokines that lead to increased apoptosis in normal cells. This phenomenon contributes to low levels of circulating