Abstract
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway has been known to be involved in cell growth, cellular differentiation processes development, immune cell survival, and hematopoietic system development. As an important member of the STAT family, STAT3 participates as a major regulator of cellular development and differentiation-associated genes. Prolonged and persistent STAT3 activation has been reported to be associated with tumor cell survival, proliferation, and invasion. Therefore, the JAK-STAT pathway can be a potential target for drug development to treat human cancers, e.g., hematological malignancies. Although STAT3 upregulation has been reported in hematopoietic cancers, protein-level STAT3 mutations have also been reported in invasive leukemias/lymphomas. The principal role of STAT3 in tumor cell growth clarifies the importance of approaches that downregulate this molecule. Epigenetic modifications are a major regulatory mechanism controlling the activity and function of STAT3. So far, several compounds have been developed to target epigenetic regulatory enzymes in blood malignancies. Here, we discuss the current knowledge about STAT3 abnormalities and carcinogenic functions in hematopoietic cancers, novel STAT3 inhibitors, the role of epigenetic mechanisms in STAT3 regulation, and targeted therapies, by focusing on STAT3-related epigenetic modifications.
Highlights
Signal transducers and activators of transcription (STATs) are a family of seven cytoplasmic transcription factors that receive the signals from cell-surface cytokine receptors and growth factor receptors and transmit them to the cell nucleus (Morris et al, 2018; Hosseini et al, 2020)
They suggested that SHP1 methylation may be an effective epigenetic factor that correlates with SOCS6 and enhances neoplastic cell growth (Sharma et al, 2019)
The detection of genetic mutations in specific enzymes involved in epigenetic regulation is invaluable
Summary
Signal transducers and activators of transcription (STATs) are a family of seven cytoplasmic transcription factors that receive the signals from cell-surface cytokine receptors and growth factor receptors and transmit them to the cell nucleus (Morris et al, 2018; Hosseini et al, 2020). The STAT proteins participate in normal cellular events, such as survival, proliferation, Epigenetics and Blood Disorders and differentiation. The signals produced by the Janus kinase (JAK)/STAT signaling pathway are essential to the blood circulatory system and immune response (Murray, 2007). Activation of cytokine receptors induces anti-apoptotic, proliferative, and differentiation signals, determining the development of different blood cell lineages (Hirano et al, 2000; Robb, 2007). The results of a study revealed that during the last reprogramming phase of the pre-induced pluripotent stem cells (pre-iPSCs), JAK/STAT3 activity plays a key role in promoting the pluripotency establishment at the epigenetic level through open-chromatin formation and facilitation of DNA demethylation/de novo methylation. We will describe other epigenetic-associated proteins such as p66a (GATAD2A) and the significance of targeting the JAK-STAT signaling pathway in leukemia treatment
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