• Turk J Med Sci · Apr 2019

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

    • Can Türk, Müfide Okay, Seyhan Türk, Elif Sena Temirci, Osama Javad, Salih Aksu, Nilgün Sayınalp, and İbrahim Celalettin Haznedaroğlu.
    • Turk J Med Sci. 2019 Apr 18; 49 (2): 661-674.

    Background/AimRuxolitinib, a JAK/STAT signaling pathway inhibitor targeted drug, has been approved for the controlling of disease symptoms and splenomegaly in patients with myeloproliferative neoplastic diseases. Recently, it has been proposed that ruxolitinib-induced 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 bioinformatics study is to detect any possible confounding effects of ruxolitinib on the genesis of lymphoproliferative disorders.Materials And MethodsThe gene expression data were retrieved from the E-MTAB-783 Cancer Genome Project database. Gene expression data for all available genes in 26 cell lines belonging to various types of lymphomas were chosen for use in this in silico analysis.ResultsWe identified genes that were significant in developing resistance to ruxolitinib in lymphoma cell lines.ConclusionBased on the results of our present study, ruxolitinib may potentially lead to the pathological expression of the transcription factors important in lymphoma genesis, neoplastic commitment on the progenitor lymphoid cells, inhibition of repressor transcriptions protective for lymphoma development, inhibition of apoptosis, promotion of neoplastic proliferation, transcriptional activation, and proliferation of malignant neoplastic B cells.

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