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BackgroundAcute myeloid leukemia (AML) is a highly heterogeneous disease. MicroRNAs function as important biomarkers in the clinical prognosis of AML.MethodsThis study identified miR-425 as a prognostic factor in AML by screening the TCGA dataset. A total of 162 patients with AML were enrolled for the study and divided into chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) groups.ResultsIn the chemotherapy group, patients with high miR-425 expression had significantly longer overall survival (OS) and event-free survival (EFS) compared with patients with low miR-425 expression. In multivariate analyses, high miR-425 expression remained independently predictive of a better OS (HR = 0.502, P = 0.005) and EFS (HR = 0.432, P = 0.001) compared with patients with low miR-425 expression. Then, all patients were divided into two groups based on the median expression levels of miR-425. Notably, the patients undergoing allo-HSCT had significantly better OS (HR = 0.302, P < 0.0001) and EFS (HR = 0.379, P < 0.0001) compared with patients treated with chemotherapy in the low-miR-425-expression group. Mechanistically, high miR-425 expression levels were associated with a profile significantly involved in regulating cellular metabolism. Among these genes, MAP3K5, SMAD2, and SMAD5 were predicted targets of miR-425.ConclusionsThe expression of miR-425 may be useful in identifying patients in need of strategies to select the optimal therapy between chemotherapy and allo-HSCT treatment regimens. Patients with low miR-425 expression may consider early allo-HSCT.

Acute myeloid leukemia (AML) is a heterogeneous disease with unfavorable outcomes. MicroRNAs (miRNAs) are important regulators and prognostic factors involved in AML. To determine the clinical role of miR-338 in AML, a total of 164 adults with de novo AML were collected. These patients were classified into a chemotherapy group and an allogeneic hematopoietic stem cell transplantation (allo-HSCT) group according to the clinical treatment, and then each group was divided into two subgroups based on the median miR-338 expression values. We found that upregulated miR-338 positively correlates with higher frequencies of complex karyotype, RUNX1 mutation, and poor risk status. In the chemotherapy group, high expression of miR-338 was independently associated with shorter EFS and OS.However, no significant differences were observed between the two subgroups within the allo-HSCT group. We also divided all patients into two groups according to the median miR-338 expression values of the whole cohort. In the miR-338 high expression group, patients receiving allo-HSCT had longer OS and EFS than those receiving chemotherapy only. In contrast, patients receiving different therapies had similar OS and EFS in the miR-338 low expression group. Our study suggests that high expression of miR-338 is an adverse prognostic biomarker in patients with AML undergoing chemotherapy and may guide treatment decisions for AML. Furthermore, allo-HSCT could significantly overcome the negative effect of high miR-338 expression, but it seemed to be unbeneficial and unnecessary for low miR-338 expressions.

Background Acute myeloid leukemia (AML) is a highly heterogeneous malignancy with various outcomes, and therefore needs better risk stratification tools to help select optimal therapeutic options. Methods In this study, we identify miRNAs that could predict clinical outcome in a heterogeneous AML population using TCGA dataset. Results We found that MiR-363 is a novel prognostic factor in AML patients undergoing chemotherapy. In multivariable analyses, high miR-363 remained predictive for shorter OS (HR = 2.349, P = 0.012) and EFS (HR = 2.082, P = 0.001) independent of other well-known prognostic factors. More importantly, allogeneic hematopoietic stem cell transplantation (allo-HSCT) overcame the adverse outcomes related to high miR-363 expression. In gene expression profiling, high miR-363 expression was positively correlated with the amounts of leukemogenic transcription factors, including Myb, RUNX3, GATA3, IKZF3, ETS1 and MLLT3. Notably, we found that the in silico predicted target genes (EZH2, KLF6 and PTEN) of miR-363 were downregulated in association with high miR-363 expression. Conclusions In summary, miR-363 expression may help identify patients in need of strategies to select the optimal therapy between chemotherapeutic and allo-HCST regimens. AML patients with high miR-363 expression may be highly recommended for early allo-HSCT regimen.

Background Acute myeloid leukemia (AML) pertains to a hematologic malignancy with heterogeneous therapeutic responses. Improvements in risk stratification in AML patients are warranted. MicroRNAs have been associated with the pathogenesis of AML. Methods To examine the prognostic value of miR-25, 162 cases with de novo AML were classified into two groups according to different treatment regimens. Results In the chemotherapy group, cases with upregulated miR-25 expression showed relatively longer overall survival (OS; P = 0.0086) and event-free survival (EFS; P = 0.019). Multivariable analyses revealed that miR-25 upregulation is an independent predictor for extended OS (HR = 0.556, P = 0.015) and EFS (HR = 0.598, P = 0.03). In addition, allogeneic hematopoietic stem cell transplantation (allo-HSCT) circumvented the poor prognosis that was related to miR-25 downregulation with chemotherapy. The expression level pattern of miR-25 coincided with AML differentiation and proliferation, which included HOXA and HOXB cluster members, as well as the HOX cofactor MEIS1. The MYH9 gene was identified as a direct target of miR-25. Conclusions The miR-25 levels are correlated with prognosis in AML independently of other powerful molecular markers. The expression of miR-25 may contribute to the selection of the optimal treatment regimen between chemotherapy and allo-HCST for AML patients.