Clinical, hematological, and immunological aspects of chronic myeloid leukemia: from molecular mechanisms to functional recovery

Authors

DOI:

https://doi.org/10.15587/2519-4798.2025.340270

Keywords:

chronic myeloid leukemia, CD26 leukemic stem cells, additional ASXL1/RUNX1/TP53 mutations, extracellular vesicles, ferroptosis, natural killer cells, PD-1, NKG2A-HLA-E, tyrosine kinase inhibitors, remission without treatment

Abstract

The aim. To systematize and critically analyze data on clinical, hematological, molecular, and immunological determinants of chronic myeloid leukemia (CML) progression and treatment-free remission (TFR) with an emphasis on the pathophysiological mechanisms of leukemic stem cells (LSCs, CD26+), additional mutations (ASXL1, RUNX1, TP53), extracellular vesicles (EVs), ferroptosis, and immune control axes (PD-1/PD-L1, NKG2A-HLA-E), as well as the immunomodulatory effects of tyrosine kinase inhibitors (TKIs).

Materials and methods. A targeted narrative review of guidelines (ELN, NCCN) and peer-reviewed publications from 2000–2025 from PubMed/PMC and specialized journals was conducted. Clinical predictors of response, pathophysiological mechanisms of resistance, and immune biomarkers of TFR success were summarized; a conceptual synthesis of evidence on the impact of different generations of TKIs on the immune landscape was performed, taking into account the post-COVID context.

Results. CD26+ LSCs determine the early dynamics of the molecular response to ITC, but their persistence during TFR is not a sufficient predictor of relapse, emphasizing the leading role of immune surveillance. Additional ASXL1/RUNX1/TP53 mutations are associated with worse event-free survival and the need for early intensification of the strategy. EVs carry oncogenic signals (in particular, BCR-ABL1 transcript) and form an immunosuppressive microenvironment. Imatinib-resistant cell models show increased sensitivity to ferroptosis inducers, opening up a new therapeutic vector. Successful TFR is associated with higher numbers and maturity of NK cells (CD56+ CD16+ CD57+), the presence of memory-like NK (NKG2C+), high perforin content in NK and innate CD8+ T cells, and simultaneously low PD-1 expression. The NKG2A-HLA-E axis acts as an additional “brake” on cytotoxicity; its blockade potentially synergizes with anti-PD-1. Dasatinib, unlike imatinib/nilotinib, partially relieves inhibition via NKG2A, enhancing NK cytotoxicity. The COVID-19 pandemic has changed patients' immune “fingerprints” (fewer NK cells with higher activation), which should be taken into account when selecting for TFR.

Conclusions. Control of CML is a balance between deep cytoreduction with ITC and competent immune surveillance. Personalized tactics should combine: early identification of high-risk mutations, targeting CD26+ LSC, modification of EV signalling and induction of ferroptosis, as well as immunotherapeutic combinations (PD-1/PD-L1 and/or NKG2A-HLA-E blockade), which can increase the proportion of patients eligible for sustained TFR and bring the concept of functional recovery closer

Author Biography

Olena Kucher, Shupyk National Healthcare University of Ukraine

Doctor of Medical Sciences, Professor

Department of Therapy, Family Medicine, Hematology and Transfusiology

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Clinical, hematological, and immunological aspects of chronic myeloid leukemia: from molecular mechanisms to functional recovery

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Published

2025-10-03

How to Cite

Kucher, O. (2025). Clinical, hematological, and immunological aspects of chronic myeloid leukemia: from molecular mechanisms to functional recovery. ScienceRise: Medical Science, (2(63), 10–16. https://doi.org/10.15587/2519-4798.2025.340270

Issue

No. 2(63) (2025)

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Medical Science

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Copyright (c) 2025 Olena Kucher

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