Acute myeloid leukemia (AML) is an aggressive blood cancer with low survival rates, which accounts for 15% of acute leukemias in children. In spite of significant advances in recent years, therapeutic options for sick children remain limited. Furthermore, identifying patients that may respond to specific therapies remains a challenge. We have identified a gene, TENT5A, that is highly expressed in tumor cells in a subset of pediatric AML patients and is associated with worse outcome. Previous work suggests that TENT5A may modulate the immune response to AML by regulating the expression of antigen presentation molecules, that allow cells to be recognized by killer T cells. In patient cells and AML-derived cell lines, cells expressing high levels of TENT5A express higher levels of antigen presentation genes, and thus may be more susceptible to recognition and killing by T cells. Here we propose to characterize the role of TENT5A in normal hematopoiesis and in AML development, and to examine its role in regulation of the immune response to AML. We also suggest that TENT5A expression may serve as a biomarker to identify patients that will benefit from immunotherapy.