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Peer-reviewedCC BYHematology, Transfusion and Cell Therapy

LONGITUDINAL EXPRESSION OF MICRORNAS IN CHRONIC MYELOID LEUKEMIA FOLLOWING TYROSINE KINASE INHIBITOR DISCONTINUATION: POTENTIAL BIOMARKERS OF TREATMENT-FREE REMISSION

  • Lilian Maria Garcia RAMOS1
  • Luciana AMBRÓSIO1
  • Vitor Leonardo BASSAN1
  • Larissa Saeei BINELLI2
  • Leonardo Carvalho PALMA3
  • Lorena Lobo Figueiredo PONTES3
  • Fabiola Attié CASTRO1
  1. 1Faculda de Ciências Farmacêuticas, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
  2. 2Faculdade de Medicina, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
  3. 3Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
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Abstract

Background and aim: Treatment-free remission (TFR) has become a major therapeutic goal in chronic myeloid leukemia (CML). However, reliable biomarkers capable of predicting sustained molecular remission after tyrosine kinase inhibitor (TKI) discontinuation remain unavailable. MicroRNAs (miRNAs) are promising candidates due to their regulatory roles in gene expression, immune responses, and leukemic stem cell persistence. This study investigated the longitudinal expression of selected miRNAs during TKI discontinuation and their association with successful TFR. Methods: This ongoing multicenter longitudinal study included 27 patients with chronic-phase CML followed at the Hospital das Clínicas, Ribeirão Preto Medical School, University of São Paulo, and the Hemocentro of the University of Campinas. Ninety-two peripheral blood samples collected at predefined time points throughout the TKI discontinuation protocol were analyzed. Expression of miR-125b, miR-181a, miR-484, miR-616, let-7e, and miR-96 was quantified by RT-qPCR using RNU24 and RNU44 as endogenous controls. Patients were classified according to clinical outcome as sustained molecular remission (REM, n = 17) or molecular relapse (REC, n = 10). Statistical analyses were performed using the Mann-Whitney, Kruskal-Wallis, and Friedman tests (p < 0.05). Patient recruitment and longitudinal follow-up are ongoing. Results: Until this moment, seventeen patients (63.0%) maintained TFR, whereas 10 (37.0%) experienced molecular relapse. No miRNA significantly discriminated REM from REC at individual time points. Nevertheless, let-7e showed a trend toward higher expression in patients who maintained TFR (p = 0.0929). Longitudinal analysis revealed distinct expression dynamics according to clinical outcome. Patients who subsequently relapsed exhibited higher miR-125b expression at the time of TKI discontinuation, suggesting that elevated baseline levels may precede molecular recurrence. Conversely, let-7e expression increased significantly between treatment discontinuation and the 12-month follow-up exclusively in patients who maintained TFR, indicating a potential association with sustained molecular control. In contrast, miR-181a, miR-484, miR-616, and miR-96 remained remarkably stable throughout follow-up regardless of clinical outcome, suggesting limited utility as dynamic biomarkers of TFR. Conclusions: Although no individual miRNA distinguished patients who maintained TFR from those who relapsed, the distinct longitudinal behavior of let-7e and miR-125b supports their biological relevance following TKI discontinuation. Increased let-7e expression during follow-up was associated with durable TFR, whereas higher miR-125b levels at discontinuation preceded molecular relapse, highlighting their potential as complementary biomarkers for patient stratification and disease monitoring. Expansion of the cohort and continued longitudinal follow-up will enable validation of these preliminary findings and further clarify the clinical utility of these miRNAs for predicting successful TKI discontinuation.

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Cite

BibTeXRIS
BibTeX
@article{ramos2026longitudinal,
  title = {{LONGITUDINAL EXPRESSION OF MICRORNAS IN CHRONIC MYELOID LEUKEMIA FOLLOWING TYROSINE KINASE INHIBITOR DISCONTINUATION: POTENTIAL BIOMARKERS OF TREATMENT-FREE REMISSION}},
  author = {Lilian Maria Garcia RAMOS and Luciana AMBRÓSIO and Vitor Leonardo BASSAN and Larissa Saeei BINELLI and Leonardo Carvalho PALMA and Lorena Lobo Figueiredo PONTES and Fabiola Attié CASTRO},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107517},
  url = {https://doi.org/10.1016/j.htct.2026.107517},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - LONGITUDINAL EXPRESSION OF MICRORNAS IN CHRONIC MYELOID LEUKEMIA FOLLOWING TYROSINE KINASE INHIBITOR DISCONTINUATION: POTENTIAL BIOMARKERS OF TREATMENT-FREE REMISSION
AU  - Lilian Maria Garcia RAMOS
AU  - Luciana AMBRÓSIO
AU  - Vitor Leonardo BASSAN
AU  - Larissa Saeei BINELLI
AU  - Leonardo Carvalho PALMA
AU  - Lorena Lobo Figueiredo PONTES
AU  - Fabiola Attié CASTRO
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107517
UR  - https://doi.org/10.1016/j.htct.2026.107517
AB  - Background and aim: Treatment-free remission (TFR) has become a major therapeutic goal in chronic myeloid leukemia (CML). However, reliable biomarkers capable of predicting sustained molecular remission after tyrosine kinase inhibitor (TKI) discontinuation remain unavailable. MicroRNAs (miRNAs) are promising candidates due to their regulatory roles in gene expression, immune responses, and leukemic stem cell persistence. This study investigated the longitudinal expression of selected miRNAs during TKI discontinuation and their association with successful TFR. Methods: This ongoing multicenter longitudinal study included 27 patients with chronic-phase CML followed at the Hospital das Clínicas, Ribeirão Preto Medical School, University of São Paulo, and the Hemocentro of the University of Campinas. Ninety-two peripheral blood samples collected at predefined time points throughout the TKI discontinuation protocol were analyzed. Expression of miR-125b, miR-181a, miR-484, miR-616, let-7e, and miR-96 was quantified by RT-qPCR using RNU24 and RNU44 as endogenous controls. Patients were classified according to clinical outcome as sustained molecular remission (REM, n = 17) or molecular relapse (REC, n = 10). Statistical analyses were performed using the Mann-Whitney, Kruskal-Wallis, and Friedman tests (p < 0.05). Patient recruitment and longitudinal follow-up are ongoing. Results: Until this moment, seventeen patients (63.0%) maintained TFR, whereas 10 (37.0%) experienced molecular relapse. No miRNA significantly discriminated REM from REC at individual time points. Nevertheless, let-7e showed a trend toward higher expression in patients who maintained TFR (p = 0.0929). Longitudinal analysis revealed distinct expression dynamics according to clinical outcome. Patients who subsequently relapsed exhibited higher miR-125b expression at the time of TKI discontinuation, suggesting that elevated baseline levels may precede molecular recurrence. Conversely, let-7e expression increased significantly between treatment discontinuation and the 12-month follow-up exclusively in patients who maintained TFR, indicating a potential association with sustained molecular control. In contrast, miR-181a, miR-484, miR-616, and miR-96 remained remarkably stable throughout follow-up regardless of clinical outcome, suggesting limited utility as dynamic biomarkers of TFR. Conclusions: Although no individual miRNA distinguished patients who maintained TFR from those who relapsed, the distinct longitudinal behavior of let-7e and miR-125b supports their biological relevance following TKI discontinuation. Increased let-7e expression during follow-up was associated with durable TFR, whereas higher miR-125b levels at discontinuation preceded molecular relapse, highlighting their potential as complementary biomarkers for patient stratification and disease monitoring. Expansion of the cohort and continued longitudinal follow-up will enable validation of these preliminary findings and further clarify the clinical utility of these miRNAs for predicting successful TKI discontinuation.
SN  - 2531-1379
SN  - 2531-1387
ER  -