Targeting Tudor domains in leukemia: epigenetic insights for drug development

Leukemia is a heterogeneous group of hematological malignancies characterized by uncontrolled proliferation and impaired differentiation of hematopoietic stem and progenitor cells. Epigenetic dysregulation is one of the critical drivers of leukemogenesis, often involving aberrant activity of chromatin-interacting proteins, such as readers, writers, and erasers. Tudor domain-containing proteins, such as SGF29, JMJD2A, 53BP1, Spindlin1, and UHRF1, play pivotal roles in leukemia progression by controlling key processes such as DNA damage response, transcriptional regulation, and RNA metabolism. Several recent efforts have aimed at pharmacologic targeting of the Tudor domain, opening a novel avenue for targeting epigenetic dysregulation. The review explores the structural characteristics of various Tudor domains, their binding preferences for specific histone modifications, and the consequences of these interactions for leukemia. By providing a comprehensive overview of current research, this review underscores the therapeutic potential of Tudor domain-targeting strategies in leukemia and emphasizes the need for further development of epigenetics-based treatment strategies to address resistance and relapse in these malignancies.