STAT6: Multidimensional analysis from hematopoietic immune regulation to pathogenesis mechanisms and therapeutic targets in hematologic malignancies

Signal Transduction and Activation of Transcription 6 (STAT6) is a key molecule in the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathway. Primarily induced by Interleukin-4(IL-4) and Interleukin-13(IL-13), STAT6 undergoes phosphorylation and translocates to the nucleus, where it regulates gene transcription. While the abnormal activation and oncogenic functions of STAT6 in various solid tumors are well documented, its precise biological role in the hematopoietic system has not yet been systematically investigated. Compared with solid tumors, STAT6 activation in hematological malignancies occurs with the Type 2 T helper cell (Th2-type) immune microenvironment that it mediates, which is probably a unique pathogenic mechanism. This review, therefore, delves into the multifunctionality of STAT6 within the hematopoietic system (including viral infection and immune regulation) and hematologic malignancies, as well as its impact on chemotherapy resistance. The aim is to provide a theoretical basis for understanding the biological functions of STAT6 and developing new therapeutic approaches.