| Objective: The applicant’s preliminary study has found that mi RNA expression profiles of AML are significant different with normal people, including mi R-10a-5p. The aim of study was to investigate the serum expression status and its relationship with the clinical characteristics at diagnosis,explore the prognostic significance of mi R-10a-5p in Acute Myeloid Leukemia(AML).Methods: Serum samples were obtained from 108 AML patients at the time of their diagnosis according to the French-American-British(FAB) criteria, and from 39 patients in CR, and from 21 patients in relapse at the third Hospital Affiliated to Soochow University Hospital between Dec 2009 and Oct 2014. There were 117 male and 51 female patients,with a median age of 51 years. Serum samples from 25 age- and sex-matched healthy subjects were collected as negative controls. Bone Marrow(BM) samples were obtained from 36 AML patients at the time of their diagnosis, and from 15 patients in CR, and from14 patients in relapse. There were 41 male and 24 female patients, with a median age of 51 years. 14 healthy BM samples were collected as normal controls. Meanwhile, AML cell lines HL-60 and HL-60/ADR were enrolled in this study. The total RNA was extracted from all samples by phenol/chloroform purification and centrifugation in isopropyl alcohol.Mi R-10a-5p expression in above-mentioned patients was detected by Taq Man RT-PCR assay. Investigating the serum expression status and explore the prognostic significance of mi R-10a-5p in AML.Results: HL-60/ADR cell line showed higher mi R-10 a expression than that in HL-60 cell line(P<0.001). The serum expression level of mi R-10a-5p was up-regulated in the new diagnosed AML group compared to healthy controls(p<0.001). In CR group, the serum expression level of mi R-10a-5p was closer to that of healthy controls(p>0.05) and showed a significantly downtrend when compared to the day of diagnosis(p<0.001).Nevertheless, the mi R-10a-5p expression was found to be significantly higher in cases with relapsed AML when compared individually to CR population(p<0.001). The same trend as those in serum was found in bone marrow(BM) mononuclear cells of AML patients at the time of diagnosis, CR and relapse. ROC curve analysis revealed that serum mi R-10a-5p could be available for a potential biomarker for discriminating AML from controls with an AUC(the areas under the ROC curve) of 0.831(95% CI: 0.753–0.91; p<0.001). When the cut-off value was set at 0.00076, the sensitivity was 79.6% and the specificity was 80%. We analyzed the correlation of mi R-10a-5p expression with clinical characteristics at time of diagnosis, our analysis failed to correlate the expression level of mi R-10a-5p with sex(p=0.837), age(p=0.687), white blood cell count(p=0.177),hemoglobin(p=0.441), platelet count(p=0.558), bone marrow(BM) blast count(p=0.177),cytogenetic abnormalities(p=0.288), CD34 positive rate(p=0.618), splenomegaly(p=0.558), NPM mut(p=0.319). However, it is worth mentioned that the CR rate after the first cycle of standard induction chemotherapy in the AML patients of high mi R-10a-5p group was lower than that in low mi R-10a-5p group(38.8% vs. 59.2%, respectively.p=0.043). AML patients with high serum mi R-10a-5p expression had both shorter OS than those with low mi R-10a-5p expression(p=0.042).Conclusion: The expression level of mi R-10a-5p in AML was significantly higher compared with those in controls,presented a dynamic change in the progression of AML,associated with leukemic burden and may act as a poor prognostic factor of AML.Furthermore, circulating mi RNAs are more accessible, which further increase their potential utility. These data suggested that mi R-10a-5p may act as a potential biomarker to improve the management of AML patients. |
PDF Full Text Request