İbrahim Celalettin HAZNEDAROĞLU, Salih AKSU, Nilgün SAYINALP, Seyhan TÜRK, Osama JAVAD, Can TÜRK, Elif Sena TEMİRCİ, Müfide OKAY

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

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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