Sclafani Serena, Pecoraro Alice, Agrigento Veronica, Troia Antonio, Di Maggio Rosario, Sacco Massimiliano, Maggio Aurelio, D'Alcamo Elena, Di Marzo Rosalba
Department of Oncology and Hematology, U.O.C. Hematology for Rare Blood and of Hematopoietic Organs Diseases, A.O. Reunited Hospitals Villa Sofia-Cervello , Palermo, Italy.
Hematol Rep. 2016 Dec 9;8(4):6678. doi: 10.4081/hr.2016.6678. eCollection 2016 Nov 2.
Increased expression of fetal hemoglobin (HbF) may ameliorate the clinical course of hemoglobinopathies. Hydroxyurea (HU) is the only inducer approved for the treatment of these diseases able to stimulate HbF production but patients' response is highly variable indicating the utility of the identification of pharmacogenomic biomarkers in order to predict pharmacological treatment efficacy. To date few studies to evaluate the role of genetic determinants in HU response have been conducted showing contradictory results. In this study we analyzed genes and γ-globin promoter in 60 alleles from 30 hemoglobinopathies patients under HU treatment to assess the role of these markers in HU response. We did not find any association between these genetic determinants and HU response. Before treatment started, the same patients were analyzed using liquid erythroid cultures in a test able to predict their response to HU. The results of our analysis confirm the absence of pharmacogenomic biomarker associated to HU response indicating that, the quantification of γ-globin mRNA fold increase remains the only method able to predict patients response to the drug.
胎儿血红蛋白（HbF）表达增加可能会改善血红蛋白病的临床病程。羟基脲（HU）是唯一被批准用于治疗这些疾病的能够刺激HbF产生的诱导剂，但患者的反应差异很大，这表明识别药物基因组生物标志物以预测药物治疗疗效具有实用性。迄今为止，很少有评估基因决定因素在HU反应中作用的研究，结果相互矛盾。在本研究中，我们分析了30例接受HU治疗的血红蛋白病患者的60个等位基因中的基因和γ-珠蛋白启动子，以评估这些标志物在HU反应中的作用。我们未发现这些基因决定因素与HU反应之间存在任何关联。在开始治疗前，使用液体红细胞培养对同一批患者进行检测，以预测他们对HU的反应。我们的分析结果证实不存在与HU反应相关的药物基因组生物标志物，这表明γ-珠蛋白mRNA增加倍数的定量分析仍然是预测患者对该药物反应的唯一方法。
