Acute myeloid leukemia (AML) is a group of heterogeneous hematological malignancies. We identified key genes as ITGAM and lncRNA ITGB2-AS1 through different bioinformatics tools. Furthermore, qPCR was performed to verify the expression level of essential genes in clinical samples. Retrospective research on 179 AML cases was used to investigate the relationship between the expression of ITGAM and the characteristics of AML. The critical gene relationship with immune infiltration in AML was estimated. The clinical validation and prognostic investigation showed that ITGAM, PPBP, and ITGB2-AS1 are highly expressed in AML (P < 0.001) and significantly associated with the overall survival in AML. Moreover, the retrospective research on 179 clinical cases showed that positive expression of ITGAM is substantially related to AML classification (P < 0.001), higher count of white blood cells (P < 0.01), and poor chemotherapy outcome (P < 0.05). Furthermore, based on grouping ITGAM as the high and low expression in TCGA-LAML profile, we found that genes in the highly expressed ITGAM group are mainly involved in immune infiltration and inflammation-related signaling pathways. Finally, we discovered that the expression level of ITGAM and lncRNA ITGB2-AS1 are not just closely related to the immune score and stromal score (P < 0.001) but also significantly positively correlated with various Immune signatures in AML (P < 0.001), indicating the association of these genes with immunosuppression in AML. The prediction of candidate drugs indicated that certain immunosuppressive drugs have potential therapeutic effects for AML. The critical genes could be used as potential biomarkers to evaluate the survival and prognosis of AML.