High expression of miR-363 predicts poor prognosis and guides treatment selection in acute myeloid leukemia

Abstract

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.

Common Genetic Aberrations Associated with Metabolic Interferences in Human Type-2 Diabetes and Acute Myeloid Leukemia: A Bioinformatics Approach

“…Another interesting observation regards the negative impact of rs1801282 on GATA3 in whole blood. GATA3 is a transcription factor with a multi-faceted role in hematopoiesis [35], while related genetic and epigenetic aberrations are strongly associated with AML development, prognosis and response to therapy [36,37]. Regarding T2D, GATA3 is considered an anti-adipogenic factor and a potential molecular therapeutic target for insulin resistance, through restoration of adipogenesis and amelioration of inflammation [38,39].…”

Identification of Acute Myeloid Leukemia Bone Marrow Circulating MicroRNAs

“…Interestingly, all the patients involved in this comparison were not grafted, which suggests that these four miRs could constitute a signature to guide the choice of the best treatment strategy, especially the utility of grafting patients at diagnosis. A recent study using a TCGA dataset identified a set of miRNAs, including miR-363, that could predict clinical outcome in a heterogeneous AML population [ 76 ]. This study confirms our results showing the high expression of circulating bone marrow miR-363 in nontransplanted patients with shorter OS and suggests that its high expression may help to identify patients recommended for an early allo-HSCT regimen.…”

MiR-340 Is a Biomarker for Selecting Treatment Between Chemotherapy and Allogeneic Transplantation in Acute Myeloid Leukemia

“…Aberrant miRNA expression has a potential prognostic value in AML (24). High amounts of miR-155 (25), miR-196b (26), miR-362 (27), miR-363 (22), and miR-551b (28) show associations with adverse clinical outcomes. Conversely, elevated amounts of miR-9 * (29), miR-34a (30), miR-181a (15), miR-193b (31), miR-212 (16) and miR-425 (14) predict favorable prognosis.…”