Among all cancer testis antigens, PRAME is in a unique position as it is not only widely expressed in various cancers but also elicits specific cellular immune responses against numerous neoplastic cells as well as against leukemia progenitor cells, plays a role in the innate immune response and possibly also the adaptive anti-tumor immune response, could enhance the ATRA treatment response as a combinational therapy, and could be targeted using a wider range of approaches including antibody- and CAR-based therapies. The gene discussed is PRAME; the disease is leukemia.