OncoTargets and Therapy (Oct 2022)

Molecular Changes in Chronic Myeloid Leukemia During Tyrosine Kinase Inhibitors Treatment. Focus on Immunological Pathways

  • Janowski M,
  • Ulańczyk Z,
  • Łuczkowska K,
  • Sobuś A,
  • Rogińska D,
  • Pius-Sadowska E,
  • Gniot M,
  • Kozłowski K,
  • Lewandowski K,
  • Helbig G,
  • Machaliński B,
  • Paczkowska E

Journal volume & issue
Vol. Volume 15
pp. 1123 – 1141

Abstract

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Michał Janowski,1,* Zofia Ulańczyk,2,* Karolina Łuczkowska,2 Anna Sobuś,2 Dorota Rogińska,2 Ewa Pius-Sadowska,2 Michał Gniot,3 Krzysztof Kozłowski,4 Krzysztof Lewandowski,3 Grzegorz Helbig,5 Bogusław Machaliński,2 Edyta Paczkowska2 1Department of Hematology and Transplantology, Pomeranian Medical University, Szczecin, Poland; 2Department of General Pathology, Pomeranian Medical University, Szczecin, Poland; 3Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznań, Poland; 4Department of Constitutional Law, Faculty of Law and Administration, Jagiellonian University in Krakow, Krakow, Poland; 5Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland*These authors contributed equally to this workCorrespondence: Edyta Paczkowska, Email [email protected]: The aim of our research was to investigate changes in the molecular background of the immune response in the chronic phase (CP) of chronic myeloid leukaemia (CML) during treatment with tyrosine kinase inhibitors (TKIs).Methods: Global gene and miRNA expression profiles were assessed using genome-wide RNA and miRNA microarray technology in bone marrow mononuclear cells. Fifty-one patients were recruited, and bone marrow samples were taken at diagnosis before treatment with TKIs and after 3, 6, and 12 months of treatment with TKIs. The largest number of upregulated genes was observed when the 0-month group (time of diagnosis) was compared to the 3-month group; 1774 genes were significantly upregulated, and 390 genes were significantly downregulated.Discussion: Upregulated biological processes according to gene ontology (GO) classification involved basic cellular processes such as cell division, cell cycle, cell–cell adhesion, protein transport, mitotic nuclear division, apoptosis, and DNA replication. Differentially expressed miRNAs were annotated using GO classification to several immunity-related processes, including the T cell receptor signalling pathway, T cell costimulation, immune response, and inflammatory response. TKI therapy exerts a significant impact on cellular cycle processes and T-cell activation, which was proven at the molecular level.Keywords: chronic myeloid leukaemia, tyrosine kinase inhibitor, immune response, gene microarrays, miRNAs

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