Journals / Turkish Journal of Medical Sciences / 2019 / Cilt: 49 - Sayı: 2

The impact of JAK/STAT inhibitor ruxolitinib on the genesis of lymphoproliferative diseases

Pages
661–674
Publication Date
2022-11-05
DOI
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Geneexpression data for all available genes in 26 cell lines belonging to various types of lymphomas were chosen for use in this in silicoanalysis.Results: We identified genes that were significant in developing resistance to ruxolitinib in lymphoma cell lines.Conclusion: Based on the results of our present study, ruxolitinib may potentially lead to the pathological expression of the transcriptionfactors important in lymphoma genesis, neoplastic commitment on the progenitor lymphoid cells, inhibition of repressor transcriptionsprotective for lymphoma development, inhibition of apoptosis, promotion of neoplastic proliferation, transcriptional activation, andproliferation of malignant neoplastic B cells.

📌 3 Key Takeaways

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Objective & Hypothesis:Background/aim: Ruxolitinib, a JAK/STAT signaling pathway inhibitor targeted drug, has been approved for the controlling of diseasesymptoms and splenomegaly in patients with myeloproliferative neoplastic diseases.
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Key Findings & Data:The aim of this bioinformaticsstudy is to detect any possible confounding effects of ruxolitinib on the genesis of lymphoproliferative disorders.Materials and methods: The gene expression data were retrieved from the E-MTAB-783 Cancer Genome Project database.
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Conclusion & Impact:Geneexpression data for all available genes in 26 cell lines belonging to various types of lymphomas were chosen for use in this in silicoanalysis.Results: We identified genes that were significant in developing resistance to ruxolitinib in lymphoma cell lines.Conclusion: Based on the results of our present study, ruxolitinib may potentially lead to the pathological expression of the transcriptionfactors important in lymphoma genesis, neoplastic commitment on the progenitor lymphoid cells, inhibition of repressor transcriptionsprotective for lymphoma development, inhibition of apoptosis, promotion of neoplastic proliferation, transcriptional activation, andproliferation of malignant neoplastic B cells.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Background/aim: Ruxolitinib, a JAK/STAT signaling pathway inhibitor targeted drug, has been approved for the controlling of diseasesymptoms and splenomegaly in patients with myeloproliferative neoplastic diseases. Recently, it has been proposed that ruxolitinibinduced JAK/STAT pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas.However, the biological basis and significance of this pharmacobiological adverse event is unknown. The aim of this bioinformaticsstudy is to detect any possible confounding effects of ruxolitinib on the genesis of lymphoproliferative disorders.Materials and methods: The gene expression data were retrieved from the E-MTAB-783 Cancer Genome Project database. Geneexpression data for all available genes in 26 cell lines belonging to various types of lymphomas were chosen for use in this in silicoanalysis.Results: We identified genes that were significant in developing resistance to ruxolitinib in lymphoma cell lines.Conclusion: Based on the results of our present study, ruxolitinib may potentially lead to the pathological expression of the transcriptionfactors important in lymphoma genesis, neoplastic commitment on the progenitor lymphoid cells, inhibition of repressor transcriptionsprotective for lymphoma development, inhibition of apoptosis, promotion of neoplastic proliferation, transcriptional activation, andproliferation of malignant neoplastic B cells.

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Cite This Article

HAZNEDAROĞLU, İ. C., AKSU, S., SAYINALP, N., TÜRK, S., JAVAD, O., TÜRK, C., TEMİRCİ, E. S., OKAY, M. (2022). The impact of JAK/STAT inhibitor ruxolitinib on the genesis of lymphoproliferative diseases. Turkish Journal of Medical Sciences, Cilt: 49 - Sayı: 2, 661–674. https://ajindex.com/articles/609946

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References (13)

  1. Shaker ME, Hazem SH, Ashamallah SA. Inhibition of the JAK/STAT pathway by ruxolitinib ameliorates thioacetamideinduced hepatotoxicity. Food and Chemical Toxicology 2016
  2. doi: 10.1016/j.fct.2016.08.018 2. Scott LM. Inhibitors of the JAK/STAT pathway, with a focus on ruxolitinib and similar agents. Communications Chemistry 2018
  3. doi: 10.1007/978-3-319-75184-9_6 3. Scott LM, Gandhi MK. Deregulated JAK/STAT signalling in lymphomagenesis, and its implications for the development of new targeted therapies. Blood Reviews 2015
  4. doi: 10.1016/j.blre.2015.06.002 4. Groner B, von Manstein V. JAK STAT signaling and cancer: opportunities, benefits and side effects of targeted inhibition. Molecular and Cellular Endocrinology 2017
  5. doi: 10.1016/j.mce.2017.05.033 5. Thomas SJ, Snowden JA, Zeidler MP, Danson SJ. The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours. British Journal of Cancer 2015
  6. doi: 10.1038/bjc.2015.233 6. Porpaczy E, Tripolt S, Hoelbl-Kovacic A, Gisslinger B, BagoHorvath Z et al. Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy. Blood 2018
  7. doi: 10.1182/blood-2017-10-810739 7. Diamantidis MD. Ruxolitinib for myelofibrosis. New England Journal of Medicine 2012
  8. doi: 10.1056/ NEJMc1203704 8. Soyer N, Haznedaroğlu İC, Cömert M, Çekdemir D, Yılmaz M et al. Multicenter retrospective analysis of Turkish patients with chronic myeloproliferative neoplasms. Turkish Journal of Hematology 2017
  9. doi: 10.4274/tjh.2016.0005 9. Eliaçık E, Işık A, Aksu S, Üner A, Büyükaşık Y et al. Pharmacobiological approach for the clinical development of ruxolitinib in myeloproliferative neoplasms. Turkish Journal of Hematology 2015
  10. doi: 10.4274/tjh.2013.0265 10. Haznedaroglu IC. Ruxolitinib for myelofibrosis. New England Journal of Medicine 2012
  11. doi: 10.1056/ NEJMc1203704 11. Saydam G. Efficacy and safety of ruxolitinib in 132 Turkish patients with myelofibrosis: a multicenter and retrospective analysis. Clinical Lymphoma, Myeloma and Leukemia 2018
  12. doi: 10.1016/j.clml.2018.07.180 12. Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A et al. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature 2012
  13. doi: 10.1038/nature11005 13. Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R et al. The GeneM