Abdel-Khalek Sara, Saleh Layla M, Abdel-Aziz Sherin, Hyder Ayman, Abdel-Ghaffar Hasan
Faculty of Science, Damietta University, Damietta, Egypt.
Oncology Center, Mansoura University, Mansoura, Egypt; Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Hematol Transfus Cell Ther. 2021 Apr-Jun;43(2):141-146. doi: 10.1016/j.htct.2020.01.002. Epub 2020 Mar 13.
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children characterized by the overproduction and accumulation of immature lymphoid cells in the bone marrow and peripheral blood. The BMI-1 is an important component of the Polycomb Repressive Complex-1 (PRC1). It is an important molecule for the self-renewal of hematopoietic stem cells (HSCs). The BMI-1 expression is generally high in HSCs and decreases after cell differentiation. The BMI-1 is required for the maintenance of normal and cancer stem cells and has been reported as an oncogene in various tumors. The NANOG is a homeodomain transcription factor responsible for maintaining the stem cell compartment at the blastocyst stage of developing embryos. The NANOG gene has been proven to be transcribed in CD34+ cells and different leukemic cells.
The ribonucleic acid (RNA) was extracted from the peripheral blood mononuclear cells (PBMNCs) of 30 pediatric ALL patients (16 B-ALL and 14 T-ALL) and 14 healthy controls. The Bmi-1 and NANOG expression levels were determined using the quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR).
Compared to normal controls, patients with ALL exhibited upregulated levels of Bmi-1 (p=0.03). Patients who overexpressed Bmi-1 and NANOG displayed a significantly worse survival than low-expressing patients (hazard ratio (HR) 5.74, 95% confidence interval (CI):1.48-22, p=0.012 and HR 3.8, 95% CI:1.009-14.3, p=0.048, respectively).
Taken together, these data suggest that the Bmi-1 and NANOG might serve as a novel survival predictor in ALL patients. Our observation also suggests that the Bmi-1 and NANOG could serve as new therapeutic targets for treatment of pediatric ALL.
急性淋巴细胞白血病（ALL）是儿童最常见的恶性肿瘤，其特征是骨髓和外周血中未成熟淋巴细胞过度产生和积聚。BMI-1是多梳抑制复合体-1（PRC1）的重要组成部分。它是造血干细胞（HSC）自我更新的重要分子。BMI-1在造血干细胞中通常高表达，细胞分化后表达降低。BMI-1是维持正常干细胞和癌症干细胞所必需的，并且在各种肿瘤中已被报道为一种癌基因。NANOG是一种同源结构域转录因子，负责在发育胚胎的囊胚阶段维持干细胞区室。NANOG基因已被证实在CD34+细胞和不同白血病细胞中表达。
从30例小儿ALL患者（16例B-ALL和14例T-ALL）及14例健康对照者的外周血单个核细胞（PBMNC）中提取核糖核酸（RNA）。使用定量实时逆转录聚合酶链反应（qRT-PCR）测定Bmi-1和NANOG的表达水平。
与正常对照相比，ALL患者的Bmi-1水平上调（p=0.03）。Bmi-1和NANOG过表达的患者比低表达患者的生存情况明显更差（风险比（HR）分别为5.74，95%置信区间（CI）：1.48-22，p=0.012；HR为3.8，95%CI：1.009-14.3，p=0.048）。
综上所述，这些数据表明Bmi-1和NANOG可能作为ALL患者新的生存预测指标。我们的观察还表明，Bmi-1和NANOG可作为小儿ALL治疗的新靶点。
