Abstract
The key cell population permits cancer cells to avoid immune-surveillance is regulatory T cells (Tregs). This study evaluates the level of Tregs in chronic myeloid leukemia (CML) patients and the effect of Tyrosine kinase inhibitor (TKI) on Treg levels, as a pathway to understand the immune response and behavior among advance stage and optimal response CML patients using imatinib therapy. Blood samples were collected from 30 CML patients (optimal response to TKI), 30 CML patients (failure response to TKI), and 30 age- and gender-matched controls. Analysis involved measuring percentages of Tregs (CD4 + CD25 + FOXP3 +) by flow cytometer and demethylation levels of FOXP3 Treg-specific demethylated region (TSDR) by PCR. The data revealed that Tregs and the FOXP3-TSDR demethylation percentages significantly increased in failure response group in comparison to the optimal response and control groups, while no significant difference between optimal response and control groups. Tregs and FOXP3 TSDR demethylation percentages showed high sensitivity and specificity, suggesting powerful discriminatory biomarkers between failure and optimal groups. An assessment of the Tregs and demethylation percentage among different BCR-ABL levels of CML patients on TKI revealed no significant differences in parameter percentage in the optimal response to TKI patients with different molecular responses (log 3 reduction or other deeper log 4.5 and 5 reduction levels). Our findings demonstrate an effective role of functional Tregs among different CML stages. Also, the study suggests that the major molecular response to therapy at level 0.1% of BCR-ABL transcript could be enough to induce immune system restoration in patients.
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All data used in current study are available from the corresponding author on reasonable request.
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Shahla’a Fadhil Sabir: methodology, conducted the laboratory work, data curation, writing—original draft, preparation, visualization, investigation, and writing—review and editing. Bassam Francis Matti: had the idea for this research, cases follow-up, supervision, and project administration. Wifaq Mahmood Ali Alwatar: supervision and project administration. All authors contributed to reviewing and revising the paper. Final approval of manuscript was done by all the authors.
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Ethics approval is sought from the scientific ethical committee of the college of medicine /Baghdad University (Date 27/2/2019 /No.365) and this study was performed in line with the principles of the Declaration of Helsinki.
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Sabir, S.F., Matti, B.F. & Alwatar, W.M.A. Assessment of regulatory T cells (Tregs) and Foxp3 methylation level in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy. Immunogenetics 75, 145–153 (2023). https://doi.org/10.1007/s00251-022-01291-4
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DOI: https://doi.org/10.1007/s00251-022-01291-4