Our study aims to: (1) reveal pan-cancer dysregulation of HOXA5 and its genomic determinants; (2) characterize its spatially resolved crosstalk with the tumor immune ecosystem; (3) establish its clinical utility as an independent prognostic biomarker in AML; and (4) identify targeted therapies against HOXA5-driven tumorigenesis. The gene discussed is HOXA5; the disease is acute myeloid leukemia.