Dover G J, Humphries R K, Young N, Ley T, Boyer S, Charache S, Nienhuis A
Prog Clin Biol Res. 1985;191:447-54.
The ease with which HbF production can be increased in subjects with SS disease was a totally unexpected phenomena on the basis of previous models of HbF synthesis. The fact that these drugs induce rapid increases in F cell production and increase HbF per F cell and HbS in non-F cells, may be important clues as to the mechanism of the action of these drugs. It is far from clear whether either one of these agents will be eventually used as therapy for subjects with SS disease. The more recent problems with cytotoxicity illustrated by HU, and the potential carcinogenic effect of 5-aza limit our ability to perform large controlled clinical trials at this time. The observation that HbF production is increased by two agents which perturb DNA replication may be important clues in understanding not only the origins of differential gamma versus beta globin gene expression but also the mechanism by which HbF is restricted to expression in only certain cells during normal erythroid maturation.
在镰状细胞病（SS病）患者中，提高HbF生成的难易程度，基于之前的HbF合成模型而言，是一种完全出乎意料的现象。这些药物能迅速增加F细胞生成，并提高每个F细胞中的HbF以及非F细胞中的HbS，这一事实可能是这些药物作用机制的重要线索。目前尚不清楚这两种药物最终是否会用于治疗SS病患者。羟基脲（HU）所显示出的细胞毒性以及5-氮杂胞苷的潜在致癌作用等近期问题，限制了我们现阶段开展大型对照临床试验的能力。两种干扰DNA复制的药物可增加HbF生成，这一观察结果可能不仅是理解γ珠蛋白基因与β珠蛋白基因差异表达起源的重要线索，也是理解在正常红系成熟过程中HbF为何仅在特定细胞中表达的机制的重要线索。
