RESUMEN
Objective: To study the expression of miRNA-181a in acute myeloid leukemia (AML) patients with normal karyotype to probe its prognosis significance. Methods: The expression level of miRNA-181a in bone marrow mononuclear cells of 120 de novo AML patients with normal karyotype was detected by real time fluorescence quantitative PCR. The direct sequencing method was used to detect IDH1, IDH2, NPM1, FLT3-ITD, DNMT3A and CEBPα mutations in CN-AML patients after PCR. The relationship between miRNA-181a expression and gene mutation, the clinical parameters and prognosis were analyzed. Results: The rates of overall surviva1 (OS) in high expression and low expression groups were 25.0 months and 15.0 months, respectively (P<0.05) . Relapse free survival (RFS) in high expression and low expression groups were 21.4 months and 11.2 months, respectively (P<0.05) . Significantly higher level hemoglobin, complete remission rate and proportion of wild type NPM1 expression in the high expression of miRNA-181a group were observed when compared with the lower expression of miRNA-181a group (P<0.05) . Multivariate Cox regression analysis showed miRNA-181a overexpression was an independent prognostic factor for CN-AML (HR=2.219, 95%CI 1.601~2.432, P=0.018) . Conclusion: Higher expression of miRNA-181a was a good prognostic factor independent of clinical parameters and high frequency gene mutations, which implicated that the miRNA-181a expression level could be used as an important prognostic indicator of AML patients with normal karyotype.
Asunto(s)
Leucemia Mieloide Aguda , Humanos , Cariotipo , MicroARNs , Mutación , Nucleofosmina , Pronóstico , Tirosina Quinasa 3 Similar a fmsRESUMEN
In this study, we confirmed that combining HHT with ACR can result in synergistic cytotoxicity to AML cells in vitro and in vivo. Combining HHT and ACR simultaneously inhibited PI3K/AKT and WNT/ß-catenin signaling in AML cells. Significant increases in growth inhibition and apoptosis were induced by an AKT inhibitor when the WNT3A gene of THP-1 cells was silenced. HHT+ACR could synergistically induce the apoptosis of CD34(+)/CD38(-) primary AML cells. These results highlight ß-catenin and AKT are promising targets for combination therapy for AML.