Ritanserin suppresses acute myeloid leukemia by inhibiting DGKα to downregulate phospholipase D and the Jak-Stat/MAPK pathway

Object Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs) is a main signaling pathway in the immune system, autoimmune disease and in many malignancies such as leukemia. Limiting this signaling pathway has so far been investigated in the treatment of some diseases such as lymphoma, and in this systematic review, we will investigate the role of this type in leukemia. Method This systematic review was written based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria and the principle of non-bias was respected. All the articles from 2014–2024 were extracted from Web of Science, PubMed and Scopus databases. We extracted the extracting inhibitors, related immunity elements, JAK/STAT kind, side signaling pathway. Results Three authors searched the database, after screening full texts, 17 articles were included. 15 inhibitory drugs for the JAK/STAT pathway were extracted in studies, which inhibit this signaling pathway in vitro and in cultured human leukemic cells. The most signaling pathways in leukemia were limited to STAT 5 and STAT 3, which were inhibited by Thymoquinone, Ritanserin, Dactocilib and Ruxolitinib. On the other hand, leukemic cells act exclusively through the JAK 2 pathway, which was specifically inhibited by Ruxolitinib and AG490. Increased apoptosis of leukemic cells and decreased cell survival was the result of monotherapy and multitherapy of these inhibitors in the studies available to us. Conclusion Inhibition of JAK/STAT pathway is associated with the reduction of leukemic cell growth and apoptosis of these types of cells, which seems to be a great therapeutic potential for clinical studies in all types of leukemia. We suggest that future studies investigate this type of treatment especially in children and evaluate our results.

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JAK/STAT signaling pathway inhibitors for leukemia therapeutic potential : a systematic review on in vitro literatures

Karimi,

Shahvari,

Ghasemi

et al. 2024

Preprint

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Background Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs) is a main signaling pathway in the immune system, autoimmune disease and in many malignancies such as leukemia. Limiting this signaling pathway has so far been investigated in the treatment of some diseases such as lymphoma, and in this systematic review, we will investigate the role of this type in leukemia. Method This systematic review was written based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria and the principle of non-bias was respected. All the articles from 2014–2024 were extracted from Web of Science, PubMed and Scopus databases. We extracted the extracting inhibitors, related immunity elements, JAK/STAT kind, side signaling pathway. Results Three authors searched the database, after screening full texts, 17 articles were included. 15 inhibitory drugs for the JAK/STAT pathway were extracted in studies, which inhibit this signaling pathway in vitro and in cultured human leukemic cells. The most signaling pathways in leukemia were limited to STAT 5 and STAT 3, which were inhibited by Thymoquinone, Ritanserin, Dactocilib and Ruxolitinib. On the other hand, leukemic cells act exclusively through the JAK 2 pathway, which was specifically inhibited by Ruxolitinib and AG490. Increased apoptosis of leukemic cells and decreased cell survival was the result of monotherapy and multitherapy of these inhibitors in the studies available to us. Conclusion Inhibition of JAK/STAT pathway is associated with the reduction of leukemic cell growth and apoptosis of these types of cells, which seems to be a great therapeutic potential for clinical studies in all types of leukemia. We suggest that future studies investigate this type of treatment especially in children and evaluate our results.

show abstract

Ritanserin suppresses acute myeloid leukemia by inhibiting DGKα to downregulate phospholipase D and the Jak-Stat/MAPK pathway

Cited by 4 publications

References 40 publications

Promoting effect and immunologic role of secretogranin II on bladder cancer progression via regulating MAPK and NF-κB pathways

Promoting effect and immunologic role of secretogranin II on bladder cancer progression via regulating MAPK and NF-κB pathways

JAK/STAT as therapeutic signaling pathway in leukemia: a systematic review on in vitro inhibitors

JAK/STAT signaling pathway inhibitors for leukemia therapeutic potential : a systematic review on in vitro literatures

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