Correlation analysis of bone marrow microvessel density and miRNA expression on drug resistance in patients with chronic myelogenous leukemia after tyrosine kinase inhibitor treatment

• Published in: Hematology (Luxembourg) 2024-12, Vol.29 (1), p.2304488-2304488
• Main Authors: Guo, Yi-Gang, Zhang, Lu-Lu, Hu, Ping, Li, Zhang-Zhi, Zhang, Rui-Bo, Lv, Xi, Yi, Qiong, Zhan, Ling-Bo, Feng, Xue-Lian
• Format: Article
• Language: English
• Subjects: Bone Marrow - pathology; Bone marrow microvessel density (MVD); chronic myelogenous leukemia (CML); drug resistance; Drug Resistance, Neoplasm - genetics; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; MicroRNAs - genetics; MicroRNAs - metabolism; Microvascular Density; miRNA; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; tyrosine kinase inhibitor (TKI); Tyrosine Kinase Inhibitors
• ISSN: 1607-8454; 1607-8454
• DOI: 10.1080/16078454.2024.2304488

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. 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. 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. MVD and the expression of miR-340 and miR-155 are closely associated with CML resistance after TKI treatment.