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

Introduction: 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 u...

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Bibliographic Details
Published in:OncoTargets and therapy 2022-10, Vol.15, p.1123-1141
Main Authors: Janowski, Michal, Ulanczyk, Zofia, Luczkowska, Karolina, Sobus, Anna, Roginska, Dorota, Pius-Sadowska, Ewa, Gniot, Michal, Kozlowski, Krzysztof, Lewandowski, Krzysztof, Helbig, Grzegorz, Machalinski, Boguslaw, Paczkowska, Edyta
Format: Article
Language:English
Subjects:
Age
Annotations
Apoptosis
Bone marrow
Cell activation
Cell adhesion
Cell cycle
Cell division
Chronic myeloid leukemia
Comparative analysis
Diagnosis
DNA biosynthesis
DNA microarrays
Gene expression
Genes
Genomes
Genomics
Immune response
Immune system
Inflammation
Kinases
Leukemia
Leukocytes (mononuclear)
Lymphocytes T
MicroRNA
MicroRNAs
miRNA
Myeloid leukemia
Nilotinib
Nuclear division
Original Research
Phenols
Protein transport
Remission (Medicine)
Signal transduction
Statistical analysis
T cell receptors
T cells
Tumors
Tyrosine
Tyrosine kinase inhibitors
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Summary:Introduction: 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 0month 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
ISSN:1178-6930
1178-6930
DOI:10.2147/OTT.S371847