Hypomethylation of isoform A significantly predicted poor survival in AML, linking to several cytogenetic and molecular abnormalities, such as t (8:21), inv (16), t (15;17), and genes mutations of DNMT3A, CEBPA, RUNX1, and WT1. Enrichment analysis disclosed that hypomethylation of isoform A was involved in the immune system, and it was further revealed that hypomethylation of isoform A was tightly associated with immune cell infiltration and could be served as a promising indicator for immunotherapy. This evidence concerns the gene CEBPA and acute myeloid leukemia.