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Acute myeloid leukemia (AML) requires refined risk stratification tools to drive decisions concerning effective therapeutic strategies. Here, genome-wide screening was carried out for identifying miRNA molecules capable of predicting treatment outcome in AML patients based on the TCGA dataset. We identified miR-340 as a prognostic factor for selecting treatment between chemotherapy and allogeneic transplantation (allo-HSCT). In multivariable analyses, low miR-340 expression independently predicted reduced OS (HR = 2.07, P = 0.004) and EFS (HR = 1.909, P = 0.01) independent of other well-known prognostic factors. Meanwhile, allo-HSCT overcome deleterious outcomes related to low miR-340. Cases administered allo-HSCT showed markedly improved OS (HR = 0.316, P < 0.0001) and EFS (HR = 0.391, P = 0.002) in comparison with those receiving chemotherapy in the low miR-340 group. Gene expression assessment revealed that elevated miR-340 amounts were negatively correlated with HOXA/HOXB cluster levels, as well as the amounts of the HOX cofactor MEIS1. Strikingly, in silico analysis pointing to HOXA10, HOXB2, and MEIS1 as miR-340 targets. The miR-340 expression may help identify cases requiring strategies for selecting the optimal therapeutic option between chemotherapy and allo-HCST. AML cases showing low miR-340 levels should be strongly considered for early allo-HSCT treatment. [ABSTRACT FROM AUTHOR]