Rochette J, Craig J E, Thein S L
MRC Molecular Haematology Unit, John Radcliffe Hospital, Headington, Oxford, UK.
Blood Rev. 1994 Dec;8(4):213-24. doi: 10.1016/0268-960x(94)90109-0.
The synthesis of fetal hemoglobin (HbF) is normally reduced to very low levels of less than 0.6% of the total hemoglobin in adults. The HbF is restricted to a sub-population of erythrocytes termed 'F-cells'; 85% of the normal adult population have 0.3% to 4.4% F-cells. The levels of HbF and F-cells vary by more than 10-fold in normal adults; family studies show that these levels are genetically controlled but the number and nature of these genetic factors are still poorly understood. HbF levels may be increased in adults in a number of inherited and acquired disorders, accompanied by an increase in both the number of F-cells and the amount of HbF per F-cell. The clinical significance of these conditions with raised HbF relates to their interaction in disorders such as sickle cell disease and beta thalassaemia in which raised levels of HbF can lead to considerable amelioration of disease severity. Study of the 'natural' mutants primarily associated with increased HbF has provided considerable insight into the understanding of the control of globin gene regulation and hemoglobin switching. Currently considerable effort is being channelled into clinical trials and the search for the 'ideal' therapeutic agents which could increase HbF in adult life with minimal drug toxicity.
胎儿血红蛋白（HbF）的合成在正常情况下会降至非常低的水平，在成年人中占总血红蛋白的比例不到0.6%。HbF局限于一类被称为“F细胞”的红细胞亚群；85%的正常成年人群体中F细胞的比例为0.3%至4.4%。正常成年人中HbF和F细胞的水平差异超过10倍；家族研究表明这些水平受基因控制，但这些遗传因素的数量和性质仍知之甚少。在一些遗传性和获得性疾病中，成年人的HbF水平可能会升高，同时F细胞数量和每个F细胞中的HbF量也会增加。这些HbF水平升高的情况的临床意义与其在镰状细胞病和β地中海贫血等疾病中的相互作用有关，在这些疾病中，HbF水平升高可导致疾病严重程度显著改善。对主要与HbF增加相关的“天然”突变体的研究为理解珠蛋白基因调控和血红蛋白转换的控制提供了相当多的见解。目前，大量精力正投入到临床试验以及寻找“理想”治疗药物中，这些药物能够在成年期增加HbF，同时药物毒性最小。
