Lavelle Donald E
Department of Medicine, University of Illinois at Chicago, Jesse Brown Veterans' Affairs Medical Center, Chicago, IL 60612, USA.
Semin Hematol. 2004 Oct;41(4 Suppl 6):3-10. doi: 10.1053/j.seminhematol.2004.08.002.
Increased levels of fetal hemoglobin (HbF) are clinically beneficial in patients with sickle cell disease. Hydroxurea fails to increase HbF in at least 25% of patients, and therefore, better drugs are needed. Recent clinical studies have shown that the DNA methyltransferase (DNMT) inhibitor decitabine effectively increased HbF in hydroxyurea-refractory patients. The rational use of DNMT inhibitors as therapeutic agents to reactivate HbF expression in patients with sickle cell disease is based on nearly 25 years of experimental evidence, reviewed in this article, that supports a fundamental role of DNA methylation in the silencing of gamma-globin gene expression in adults.
胎儿血红蛋白（HbF）水平升高对镰状细胞病患者具有临床益处。羟基脲至少在25%的患者中无法提高HbF水平，因此需要更好的药物。最近的临床研究表明，DNA甲基转移酶（DNMT）抑制剂地西他滨可有效提高对羟基脲耐药患者的HbF水平。本文回顾了近25年的实验证据，这些证据支持DNA甲基化在成人γ珠蛋白基因表达沉默中起基本作用，在此基础上，合理使用DNMT抑制剂作为治疗药物来重新激活镰状细胞病患者的HbF表达。
