Although further studies are needed to identify further key components and specifically characterize the cascade of events by which CD84 can regulate NRF2 degradation, to the best of our knowledge, we show for the first time that CD84 plays an essential role in regulating AML metabolism and oxidative phosphorylation, highlighting a dependency of AML to CD84 expression. This evidence concerns the gene NFE2L2 and acute myeloid leukemia.