The downregulation of these critical genes (e.g., CLEC11A, ICAM4, ITGA4, and AVP) and their pathways in AML is not merely indicative of the disease’s pathology but may also serve as negative biomarkers, which could provide valuable insights into the disease’s severity, progression, and responsiveness to treatment. This evidence concerns the gene ICAM4 and acute myeloid leukemia.