Objective: To investigate the relationship between IGF2BP3 gene expression and prognosis in patients with acute myeloid leukemia (AML).
Methods: High throughput transcriptome sequencing was performed on bone marrow primary leukemia cells from 27 patients with AML in our center, the relationship between IGF2BP3 expression levels and clinical characteristics were analyzed and verify the samples from patients with newly treated AML and refractory AML. The expression level of IGF2BP3 gene were analyzed in 20 healthy subjects and 26 patients with AML. The expression of IGF2BP3 in two anthracycline-resistant cell lines (HL60/ADR, K562/ADR) was detected by RT-qPCR and Western blot, and the expression difference of IGF2BP3 was compared with that in sensitive cells (HL60, K562). The relationship between the expression level of IGF2BP3 in patients with AML and prognostic were analyzed through data analysis of 746 patients with AML, and the prognostic value of IGF2BP3 in AML was analyzed by multivariate Cox regression analysis.
Results: In the bone marrow primary leukemia cells of 27 AML patients in our center, the expression level of IGF2BP3 in patients with refractory AML was significantly higher than that in chemotherapy sensitive patients (P =0.0343). The expression of IGF2BP3 in leukemia patients with extramedullary infiltration (EMI) was significantly higher than that in AML patients without extramedullary infiltration (P =0.0049). Compared with healthy subjects (n=20), IGF2BP3 expression in AML patients (n=26) was higher (P =0.0009). The expression of IGF2BP3 mRNA in the anthracycline resistant cell lines (HL60/ADR, K562/ADR) was significantly higher than that in the sensitive cell lines (K562/ADR vs K562,P =0.0430; HL60/ADR vs HL60, P =0.7369). Western blot results showed that the expression of IGF2BP3 protein in mycin resistant cells was significantly higher than that in sensitive cells (P < 0.001). qPCR results showed that the expression level of IGF2BP3 mRNA in refractory AML patients was significantly higher than that in patients with chemotherapy sensitive (P =0.002). High expression of IGF2BP3 was associated with poor prognosis in AML (P < 0.05) in 3 large sample cohorts of AML patients. Univariate and multivariate prognostic analyses demonstrated that high expression of IGF2BP3 was significantly associated with shorter event-free survival (EFS, HR=1.887, P =0.024) and overall survival (OS, HR=1.619, P =0.016).
Conclusion: The high expression of IGF2BP3 gene may be an important factor in the poor prognosis of AML, suggesting that IGF2BP3 gene may be a new molecular marker for the clinical prognosis evaluation and treatment strategy of AML.
题目: IGF2BP3基因表达水平在急性髓系白血病患者中的预后价值.
目的: 探寻IGF2BP3基因表达水平与急性髓系白血病（AML）患者预后的关系。.
方法: 通过对本中心27例AML患者骨髓原代白血病细胞进行转录组高通量测序，分析IGF2BP3基因表达水平与患者临床特征之间的关系，并在初治AML患者及难治AML（Refractory AML）患者样本中验证。分析20例健康对照者和26例AML患者中IGF2BP3基因表达水平的差异。采用RT-qPCR、Western blot检测两种蒽环类耐药细胞系（HL60/ADR、K562/ADR）中IGF2BP3表达水平，比较其与敏感细胞（HL60、K562）的表达差异。通过3个数据集，分析IGF2BP3在AML患者中的表达水平及与预后的关系，进一步使用Cox生存分析IGF2BP3在AML中的预后价值。.
结果: 在本中心27例AML患者骨髓原代白血病细胞中，难治性AML患者的IGF2BP3表达量明显高于化疗敏感的患者（P =0.0343），白血病细胞髓外浸润（extramedullary infiltration,EMI）患者的IGF2BP3表达量明显高于无髓外浸润的AML患者（P =0.0049）。与健康人比较，IGF2BP3在AML患者中表达增加（P =0.0009）。蒽环类耐药细胞系（HL60/ADR、K562/ADR）中IGF2BP3 mRNA的表达显著高于敏感细胞系（K562/ADR vs K562, P =0.0430; HL60/ADR vs HL60, P =0.7369）。Western blot结果显示，耐药细胞中IGF2BP3蛋白表达显著高于敏感细胞（P <0.001）。qPCR结果显示，难治AML患者中IGF2BP3的mRNA表达水平明显高于化疗敏感患者（P =0.002）。在3个大样本AML患者队列中IGF2BP3高表达预示AML预后不良（P <0.05）。单因素和多因素预后分析证实IGF2BP3高表达与患者较短的无事件生存（HR=1.887，P =0.024）和总体生存（HR=1.619，P =0.016）显著相关。.
结论: IGF2BP3基因高表达可能是AML预后不良的重要因素，提示IGF2BP3基因有望成为AML的临床预后评估和提供治疗策略的新的分子标志物。.
Keywords:
acute myeloid leukemia;