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Updated: Aug 25, 2025

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

18.2K

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

Michał Janowski1, Zofia Ulańczyk2, Karolina Łuczkowska2

  • 1Department of Hematology and Transplantology, Pomeranian Medical University, Szczecin, Poland.

Oncotargets and Therapy
|October 14, 2022
PubMed
Abstract

Insights

Tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukaemia (CML) significantly alters molecular immune responses. Gene and miRNA expression changes reveal impacts on cell cycle and T-cell activation during CML treatment.

Area of Science:

  • Hematology
  • Molecular Biology
  • Immunology

Background:

  • Chronic myeloid leukaemia (CML) is a myeloproliferative neoplasm.
  • Tyrosine kinase inhibitors (TKIs) are the standard treatment for CML.
  • Understanding the molecular effects of TKIs on the immune system is crucial.

Purpose of the Study:

  • To investigate molecular changes in the immune response during TKI treatment for CML.
  • To analyze gene and microRNA (miRNA) expression profiles in CML patients undergoing TKI therapy.

Main Methods:

  • Genome-wide RNA and miRNA microarrays were used.
  • Bone marrow mononuclear cells from 51 CML patients were analyzed.
  • Samples were collected at diagnosis and at 3, 6, and 12 months of TKI treatment.

Main Results:

  • Significant upregulation and downregulation of numerous genes were observed after 3 months of TKI therapy.
  • Gene ontology analysis revealed impacts on cell division, cell cycle, apoptosis, and DNA replication.
  • miRNA analysis indicated effects on T cell receptor signaling, T cell costimulation, and immune/inflammatory responses.

Conclusions:

  • TKI therapy profoundly impacts cellular cycle processes and T-cell activation at a molecular level in CML.
  • These findings provide molecular insights into the immune system's response to CML treatment.
Keywords:
chronic myeloid leukaemiagene microarraysimmune responsemiRNAstyrosine kinase inhibitor

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