Issa Jean-Pierre J, Byrd John C
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Semin Hematol. 2005 Jul;42(3 Suppl 2):S43-9. doi: 10.1053/j.seminhematol.2005.05.005.
5-Aza-2'-deoxycitidine (decitabine, Dacogen, Bloomington, MN) is a cytosine analogue that promotes hypomethylation of DNA and has documented efficacy in myeloid malignancies. Indeed, promising clinical results have been observed in acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS). Aberrant methylation has also been found in chronic leukemias, providing a rationale for investigating the use of decitabine in these diseases. There is clear evidence of molecular (hypomethylation) as well as hematologic and cytogenetic responses to decitabine in chronic myelogenous leukemia of all phases, including in patients resistant to imatinib mesylate. Clinical trials of decitabine in chronic lymphocytic leukemia are ongoing. There are many unanswered questions regarding optimizing this treatment for chronic leukemias, but successful proof-of-concept studies for hypomethylating agents move us closer to approaches that may have a significant impact on patient outcomes.
5-氮杂-2'-脱氧胞苷（地西他滨，达珂，明尼苏达州布鲁明顿市）是一种胞嘧啶类似物，可促进DNA去甲基化，并且在髓系恶性肿瘤中已证实具有疗效。事实上，在急性髓系白血病（AML）和骨髓增生异常综合征（MDS）中已观察到有前景的临床结果。在慢性白血病中也发现了异常甲基化，这为研究地西他滨在这些疾病中的应用提供了理论依据。有明确证据表明，在各期慢性粒细胞白血病中，包括对甲磺酸伊马替尼耐药的患者，地西他滨可引发分子水平（去甲基化）以及血液学和细胞遗传学反应。地西他滨治疗慢性淋巴细胞白血病的临床试验正在进行中。关于优化慢性白血病的这种治疗方法，仍有许多未解决的问题，但甲基化抑制剂成功的概念验证研究使我们更接近可能对患者预后产生重大影响的治疗方法。
