Many studies have demonstrated that microRNA-210 (miR-210) expression is intensively upregulated in hypoxic states and differentially regulated in most types of cancer cells. However, the clinical significance of miR-210 and its effects on the response of leukemic cells to chemotherapeutic drugs in childhood acute lymphoblastic leukemia (ALL) remain unknown. In the current study, using real-time qRT-PCR to detect miR-210 expression in bone marrow samples from 114 children at initial diagnosis of ALL, we investigated the prognostic significance of miR-210 and determined its associations with common clinical characteristics and treatment outcome. We further examined its effect on the response to chemotherapeutic drugs in the Reh and RS4;11 cell lines. Results showed that miR-210 expression was significantly lower in patients suffering from relapse and induction failure than in other patients (P < 0.001). Using the receiver operating characteristic curve, 3.8243 was selected as the cut-off value of miR-210 expression in our test cohort (38 cases). A significantly poorer treatment outcome (P < 0.05) was found in the low-expression group and verified in the validation cohort (76 cases, P < 0.05). Patients with low expression of miR-210 and positive minimal residual disease at the end of induction had a much higher rate of relapse or induction failure (P = 0.001). Increasing/decreasing miR-210 expression using agomir/antagomir could enhance or reduce the response of Reh cells and RS4;11 cells to daunorubicin/dexamethasone/L-asparaginase and daunorubicin/dexamethasone/vincristine, respectively. In conclusion, miR-210 may be a good prognostic factor and a useful predictor of drug sensitivity, and is a potential therapeutic target for pediatric ALL.
The prognostic significance of microRNA (miR)-210 and the caspase 8-associated protein 2 () gene in children with acute lymphoblastic leukemia (ALL) has been validated and has been demonstrated as a target of miR-210. In the present study, the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine miR-210 and expression in 91 children with ALL. Associations between gene expression levels and the prognostic value of combined detection of the two indicators were analyzed. Results from a receiver operating characteristic curve demonstrated that threshold values of miR-210 and were 3.8243 and 0.4760, respectively. Although the expression of miR-210 and were not associated at the mRNA level in pediatric ALL, combined detection of the two predicted ALL prognosis with an increased accuracy. Furthermore, an equation was devised including minimal residual disease at day 33 and expression of miR-210 and , which may enable bone marrow relapse to be predicted more precisely compared with the current risk stratification.
Low expression of E2F3a was associated with inferior prognosis in childhood ALL. An algorithm composed of E2F3a expression and MRD could predict relapse or induction failure more precisely than that of the current risk stratification.
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