Saba Hussain I, Wijermans Pierre W
Department of Internal Medicine, University of South Florida College of Medicine, James A Haley Veterans Hospital, Tampa, FL 33612, USA.
Semin Hematol. 2005 Jul;42(3 Suppl 2):S23-31. doi: 10.1053/j.seminhematol.2005.05.009.
Myelodysplastic syndromes (MDS) are a heterogenous group of hematopoietic stem cell disorders that are multifactorial in their etiology. Aberrant DNA hypermethylation is now thought to be involved in MDS, as numerous tumor-suppressor genes have been identified that are silenced in these patients. Thus, the use of DNA methyltransferase inhibitors, such as 5-aza-2'-deoxycytidine (decitabine, Dacogen, MGI Pharma Inc, Bloomington, MN), for reversal of this process appears to be a rational intervention that may influence the course of the disease. Several phase I/II studies have been conducted using a low-dose schedule of decitabine in MDS patients. Based on these studies, decitabine appears to be effective and generally well tolerated, especially in those patients with worse prognostic indicators. Recent results of a phase III study also confirmed that patients treated with decitabine compared to standard supportive care had higher overall response rates and longer time to AML transformation. Decitabine appears to be a promising new therapy for the treatment of MDS; however, defining the optimal dosing schedule and exploring the possible use in combination with other agents such as the histone deacetylase inhibitors need further evaluation.
骨髓增生异常综合征（MDS）是一组异质性造血干细胞疾病，其病因是多因素的。目前认为异常的DNA高甲基化与MDS有关，因为在这些患者中已鉴定出许多沉默的肿瘤抑制基因。因此，使用DNA甲基转移酶抑制剂，如5-氮杂-2'-脱氧胞苷（地西他滨，达珂，MGI制药公司，明尼苏达州布卢明顿）来逆转这一过程似乎是一种合理的干预措施，可能会影响疾病的进程。已经在MDS患者中使用低剂量地西他滨进行了几项I/II期研究。基于这些研究，地西他滨似乎是有效的，并且通常耐受性良好，尤其是在那些预后指标较差的患者中。一项III期研究的最新结果也证实，与标准支持治疗相比，接受地西他滨治疗的患者具有更高的总体缓解率和更长的AML转化时间。地西他滨似乎是一种有前途的治疗MDS的新疗法；然而，确定最佳给药方案并探索与其他药物如组蛋白去乙酰化酶抑制剂联合使用的可能性需要进一步评估。
