Tyrosine Kinase Inhibition in Chronic Myeloid Leukemia

Chronic myeloid leukaemia (CML) is driven by the BCR-ABL1 fusion oncoprotein, a constitutively active non-receptor tyrosine kinase arising from the Philadelphia chromosome translocation. The advent of tyrosine kinase inhibitors (TKIs), beginning with imatinib, has transformed CML from a fatal disorder into a chronic condition with near-normal life expectancy. Second- and third-generation TKIs (dasatinib, nilotinib, bosutinib and ponatinib) were developed to overcome resistance and intolerance, each displaying distinct potency and safety profiles. Deep molecular response (DMR) has become a key therapeutic goal, enabling treatment-free remission (TFR) in selected patients. Persistent leukaemia stem cells (LSCs) and kinase-independent survival pathways pose challenges to eradication and long-term cure. Ongoing efforts focus on novel targets to eliminate LSCs, refine biomarkers for safe discontinuation, mitigate cardiovascular and other adverse events, and personalise TKI selection according to patient risk, comorbidities and treatment objectives.

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Tyrosine Kinase Inhibition in Chronic Myeloid Leukemia publication trend

The graph below shows the total number of articles in tyrosine kinase inhibition in chronic myeloid leukemia across all publications each year (not limited to Nature Index journals).

Technical terms

Tyrosine kinase inhibitor (TKI): A small-molecule drug that selectively inhibits the enzymatic activity of tyrosine kinases such as BCR-ABL1.

BCR-ABL1: A fusion gene encoding a constitutively active tyrosine kinase formed by the Philadelphia chromosome translocation t(9;22).

Deep molecular response (DMR): A profound reduction in BCR-ABL1 transcript levels, typically defined as MR4 or deeper, indicating minimal residual disease.

Treatment-free remission (TFR): A sustained absence of molecular relapse after discontinuation of TKI therapy.

Leukaemia stem cell (LSC): A subpopulation of CML cells with self-renewal capacity that can regenerate disease and persists despite TKI therapy.

References

1. TSPAN32 suppresses chronic myeloid leukemia pathogenesis and progression by stabilizing PTEN. Signal Transduction and Targeted Therapy (2023).
2. Elevated plasma levels of IL-6 and MCP-1 selectively identify CML patients who better sustain molecular remission after TKI withdrawal. Journal of Hematology & Oncology (2023).
3. Cardiovascular Toxicity of Tyrosine Kinase Inhibitors Used in Chronic Myeloid Leukemia: An Analysis of the FDA Adverse Event Reporting System Database (FAERS). Cancers (2020).
4. Chronic myeloid leukemia stem cells. Leukemia (2019).
5. Tyrosine Kinase Inhibitors Available for Chronic Myeloid Leukemia: Efficacy and Safety. Frontiers in Oncology (2019).