JAK-STAT pathway in hematological malignancies: Achievements, challenges and future perspectives

Over the past few decades, the JAK-STAT signaling pathway has emerged as a focal point in the fields of cell biology and pathology. This pathway is considered one of the central communication nodes in cellular function, playing a crucial role in processes such as cell proliferation, differentiation, survival, and apoptosis. It also mediates immune dysregulation and tumor development. Dysregulated JAK-STAT signaling pathways and associated gene mutations are closely implicated in the development and progression of hematologic malignancies. Therefore, in-depth research into the regulatory mechanisms of the JAK-STAT signaling pathway and the discovery of new therapeutic targets are of great significance for the development of safer and more effective treatment strategies. Currently, the field of JAK-STAT signaling in the treatment of hematological malignancies is rapidly evolving, making it necessary to summarize this rapidly changing area so that clinicians can promptly access new strategies for disease treatment. In this review, we have revisited the current understanding of the composition, activation, and regulation of the JAK-STAT pathway and elucidated the relationship between JAK-STAT signaling components and hematological malignancies. The review also focuses on introducing currently FDA-approved and preclinical drugs designed to target this pathway, as well as discussing the current challenges and directions in this field.