Immunity in acute myeloid leukemia: where the immune response and targeted therapy meet

Acute myeloid leukemia (AML) is a highly aggressive disease with high relapse and mortality rates. Recent years have shown a surge in novel therapeutic development for AML, both in clinical and preclinical stages. These developments include targeted therapies based on AML specific molecular signatures as well as more general immune modulation and vaccination studies. We developed a kinase inhibitor as an experimental drug for AML. We demonstrated its direct cytotoxic activity in leukemia cells via robust activation of p53 together with transcriptional elimination of several cell viability protectors. Surprisingly, we have recently realized that anti-leukemic activity of the inhibitor requires active involvement of the immune system, particularly of T cells. Treatment of mice bearing leukemia resembling a human disease generates immune memory which is sufficient to protect mice from a secondary leukemic challenge. This memory is specific, as no protection is generated against a different leukemia type. We are further investigating the link between the direct cell cytotoxicity effect of the drug and immune contribution to AML therapy. Improved understanding of the immune involvement in various stages of AML and the crosstalk between immune effectors, targeted therapy and AML cells can provide a better framework for designing the next generation of AML therapies.