Epigenetic maintenance strategies after allogeneic stem cell transplantation in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive blood malignancy characterized by the accumulation of immature blood cells that can severely impede the normal functions of the hematopoietic system. AML still has a poor 5-year survival rate of around 30%, and efforts to develop novel targeted therapies have been met with challenges. Allogeneic hematopoietic stem cell transplantation represents a potentially curative treatment for many AML patients. Donor immune cells, namely, T cells and NK cells, can help eliminate residual leukemia cells through the beneficial graft-versus-leukemia (GVL) effect. Nevertheless, malignant cells can still escape allogeneic immune surveillance and lead to disease relapse. Recent studies have provided insights into AML-specific immune evasion mechanisms, many of which are driven by epigenetic changes. This article describes epigenetic regulators as promising therapeutic targets for designing posttransplant maintenance therapies. Therefore, this review aims to summarize AML immune evasion mechanisms with a focus on the allogeneic immune environment. We discuss the roles of epigenetic regulators in driving immune escape and propose targeted strategies for preventing leukemia relapse. We then discuss the diverse immunomodulatory effects of epigenetic inhibitors and their potential to enhance the GVL effect. The current landscape of maintenance therapy trials with epigenetic inhibitors and their clinical prospects is also assessed.