Considering the highly immunosuppressive surrounding as well as the stated low immune-checkpoint-expression baseline in AML [86,87], which presumably hamper efficaciousness of CPI administration of hypomethylating agents (HMA), which promote anti-leukemic immune-response by upregulation of cellular reactivity and checkpoint-molecule expression [88,89] could be a valuable approach to ameliorate therapeutic response to CPI in AML Combined checkpoint blockades inhibiting PD-(L)1 and CTLA-4 or Tim-3 administered together with HMA are currently under investigation (NCT02530463, NCT03066648). This evidence concerns the gene HAVCR2 and acute myeloid leukemia.