National Institute of Blood Diseases and Bone Marrow Transplantation.
Omair Sana Foundation.
J Pediatr Hematol Oncol. 2022 Jan 1;44(1):e77-e83. doi: 10.1097/MPH.0000000000002136.
Despite high prevalence and incidence of β-thalassemia in Pakistan, there is very limited work on the use of hydroxyurea (HU) in thalassemia patients in the country. This is the first insight regarding genetic profiling of BCL11A and HU responses in Pakistani β-thalassemia. It correlates single-nucleotide polymorphisms on BCL11A (rs4671393, rs766432) and HBG2 (XmnI), age at first transfusion, and β-globin mutations with HU response in β-thalassemia major (BTM). Of 272 patients treated with HU, 98 were complete responders, 55 partial responders, and 119 nonresponders. Our analysis shows that HU response was significantly associated with patients having IVSI-1 or CD 30 mutation (P<0.001), age at first transfusion >1 year (P<0.001), and with the presence of XmnI polymorphism (P<0.001). The single-nucleotide polymorphisms of BCL11A were more prevalent among responders, but could not show significant association with HU response (P>0.05). Cumulative effect of all 5 predicting factors through simple binary scoring indicates that the likelihood of HU response increases with the number of primary and secondary genetic modifiers (P<0.001). Predictors scoring is a pragmatic tool to foresee HU response in patients with BTM. The authors recommend a score of ≥2 for starting HU therapy in Pakistani patients with BTM.
尽管巴基斯坦β-地中海贫血的患病率和发病率很高，但该国在β-地中海贫血患者使用羟基脲（HU）方面的工作非常有限。这是首次对巴基斯坦β-地中海贫血患者的 BCL11A 基因谱和 HU 反应进行深入了解。它将 BCL11A 上的单核苷酸多态性（rs4671393、rs766432）和 HBG2（XmnI）、首次输血年龄和β-珠蛋白突变与β-地中海贫血重型（BTM）中 HU 的反应相关联。在接受 HU 治疗的 272 名患者中，98 名是完全反应者，55 名是部分反应者，119 名是无反应者。我们的分析表明，HU 反应与患者具有 IVSI-1 或 CD30 突变（P<0.001）、首次输血年龄>1 岁（P<0.001）和存在 XmnI 多态性（P<0.001）显著相关。BCL11A 的单核苷酸多态性在反应者中更为普遍，但与 HU 反应无显著相关性（P>0.05）。通过简单的二元评分对所有 5 个预测因素的累积效应表明，HU 反应的可能性随着主要和次要遗传修饰因子数量的增加而增加（P<0.001）。预测因子评分是预测 BTM 患者 HU 反应的实用工具。作者建议在巴基斯坦 BTM 患者中，HU 治疗的起始评分≥2 分。
