Steinberg Martin H, Kumar Sara, Murphy George J, Vanuytsel Kim
Department of Medicine, Division of Hematology/Oncology, Center of Excellence for Sickle Cell Disease and Center for Regenerative Medicine, Boston University School of Medicine and Boston Medical Center, Boston MA.
Expert Rev Precis Med Drug Dev. 2019;4(6):357-367. doi: 10.1080/23808993.2019.1688658. Epub 2019 Nov 7.
Sickle cell anemia is a mendelian disease that is noted for the heterogeneity of its clinical expression. Because of this, providing an accurate prognosis has been a longtime quest.
Reviewed are the benefits and shortcomings of testing for the major modulators of the severity of disease, like fetal hemoglobin and α thalassemia, along with studies that have attempted to link genetic variation with sub-phenotypes of disease in a predictive fashion. Induced pluripotent stem cells driven to differentiate into erythroid precursor cells provide another area for potential patient-specific drug testing.
Fetal hemoglobin is the strongest modulator of sickle cell anemia but simply measuring its blood levels is an insufficient means of forecasting an individual's prognosis. A more precise method would be to know the distribution of fetal hemoglobin levels across the population of red cells, an assay not yet available. Prognostic measures have been developed using genetic and other signatures, but their predictive value is suboptimal. Widely applicable assays must be developed to allow a tailored approach to using the several new treatments that are likely to be available in the near future.
镰状细胞贫血是一种孟德尔疾病，其临床表型具有异质性。因此，长期以来一直在寻求提供准确的预后评估。
本文回顾了检测疾病严重程度的主要调节因子（如胎儿血红蛋白和α地中海贫血）的利弊，以及试图以预测方式将基因变异与疾病亚表型联系起来的研究。诱导多能干细胞分化为红系前体细胞为潜在的患者特异性药物测试提供了另一个领域。
胎儿血红蛋白是镰状细胞贫血最强的调节因子，但仅测量其血液水平不足以预测个体的预后。更精确的方法是了解胎儿血红蛋白水平在红细胞群体中的分布情况，而目前尚无此类检测方法。已经利用基因和其他特征开发了预后评估方法，但其预测价值并不理想。必须开发广泛适用的检测方法，以便能够采用量身定制的方法来使用近期可能出现的几种新疗法。
