The impact of JAK/STAT inhibitor ruxolitinib on the genesis of lymphoproliferative diseases
Date
2019Author
Turk, Can and Okay, Mufide and Turk, Seyhan and Temirci, Elif Sena and
Javad, Osama and Aksu, Salih and Sayinalp, Nilgun and Haznedaroglu,
Ibrahim Celalettin
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Background/aim: Ruxolitinib, 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 methods: The 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.
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 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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