■本研究分析了酪氨酸激酶抑制剂(TKI)治疗后骨髓微血管密度(MVD)与慢性粒细胞白血病(CML)耐药的四种miRNAs表达之间的关系。
■234例CML患者根据5年随访结果分为耐药组和非耐药组。根据TKI反应将患者分为最佳反应组和警告/失败组。通过免疫组织化学测定MVD,和四个miRNA的表达水平(miR-106a,miR-155,miR-146a,通过qPCR检查骨髓活检标本中的miR-340)。我们评估了MVD与4种miRNA的相关性,以及它们对TKI治疗后CML抵抗的预测价值。
■MVD和miR-106a的水平,miR-155和miR-146a在抗性组中显著高于非抗性组,而miR-340水平低于非抗性组。此外,MVD与miR-340和miR-155水平存在显著相关性。根据生存分析结果,MVD以及miR-340和miR-155水平与无TKI耐药患者的5年生存率显著相关。ROC曲线结果表明,miR-106a,miR-340和miR-155对TKI治疗后的CML耐药具有良好的预测准确性。至于多变量分析的结果,疾病阶段,风险水平(高风险),高MVD,miR-340低表达,miR-155高表达均为CML耐药的独立危险因素。
■MVD以及miR-340和miR-155的表达与TKI治疗后的CML耐药密切相关。
UNASSIGNED: This study analyzed the relationship between bone marrow microvessel density (MVD) and the expression of four miRNAs with chronic myelogenous leukemia (CML) resistance after tyrosine kinase inhibitor (TKI) treatment.
UNASSIGNED: 234 CML patients were divided into resistance and non-resistance groups in terms of the results of the 5-year follow-up. Patients were divided into the Optimum response group and the Warning/Failure group based on TKI response. MVD was determined by immunohistochemistry, and the expression levels of four miRNAs (miR-106a, miR-155, miR-146a, and miR-340) in bone marrow biopsy specimens were examined by qPCR. We evaluated the association of MVD with four miRNAs and them predictive value for CML resistance after TKI treatment.
UNASSIGNED: The MVD and the levels of miR-106a, miR-155, and miR-146a were significantly higher while the miR-340 level was lower in the resistance group than the non-resistance group. Besides, MVD had a significant correlation with the levels of miR-340 and miR-155. According to the results of survival analysis, MVD as well as miR-340 and miR-155 levels were observably correlated with 5-year survival of patients without TKI resistance. The results of the ROC curve indicated that the MVD, miR-106a, miR-340, and miR-155 had good predictive accuracy for CML resistance after TKI treatment. As for the results of multivariate analysis, disease stage, risk level (high risk), high MVD, low miR-340 expression, and high miR-155 expression were all independent risk factors for CML resistance.
UNASSIGNED: MVD and the expression of miR-340 and miR-155 are closely associated with CML resistance after TKI treatment.