The structure and functions of TRAF families and recent advances of TRAFs in leukemia

Leukemia is a malignant clonal disease of hematopoietic stem cells. Currently, primary treatments include chemotherapy, targeted drugs, hematopoietic stem cell transplantation, and immunotherapy. Although advances in treatment have improved survival for leukemia patients, treatment failure still occurs in some individuals for various reasons. This necessitates the discovery of new pathogenic mechanisms and the exploration of novel biological targets. Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are a family of cytoplasmic adapter proteins, typically comprising seven members. The TRAF protein family is widely involved in cell proliferation, differentiation, survival, and apoptosis, and also regulates immune and inflammatory responses. TRAFs perform dual roles in a broad range of biological activities-as adapter proteins and as E3 ubiquitin ligases-both essential for activating receptor-mediated signaling. In recent years, growing evidence has highlighted the significant role of TRAFs in leukemia, linking them to leukemic stem cell activity, drug resistance, apoptosis, and autophagy. This review introduces the functions and characteristics of TRAFs and summarizes research progress on their involvement in leukemia, underscoring their potential as novel therapeutic targets for the disease.