The PD1 Molecule May Contribute to Lower Treatment-Free Remission Rates in Patients with Chronic Myeloid Leukemia
Paulina Kwaśnik1, Michał Kiełbus1, Joanna Zaleska1
1Department of Experimental Hematooncology, Medical University of Lublin, 20-093 Lublin, Poland.
Journal of Clinical Medicine
|April 12, 2025
Summary
Chronic myeloid leukemia (CML) patients with e14a2 transcripts show distinct immune profiles compared to e13a2 variants, impacting treatment-free remission (TFR) success. These immunological differences may influence CML recurrence after therapy withdrawal.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Chronic myeloid leukemia (CML) is driven by the BCR::ABL1 fusion gene, with e14a2 and e13a2 being common variants.
- Transcript type in CML may influence the ability to achieve treatment-free remission (TFR).
Purpose of the Study:
- To immunologically characterize CML patients with e13a2 and e14a2 transcripts.
- To identify immune differences that may affect remission achievement post-therapy withdrawal.
Main Methods:
- Multicolor flow cytometry analyzed immune system differences in 51 CML patients at imatinib discontinuation and early TFR.
- RQ-PCR and ddPCR monitored BCR::ABL1 transcript dynamics.
- Principal component analysis (PCA) and k-means clustering grouped patients based on immune cell populations.
Main Results:
- PCA separated CML patients into two distinct clusters, revealing significant heterogeneity.
- A significant association was found between patient clusters and BCR::ABL1 transcript types (e13a2 vs. e14a2).
- Cluster 1 showed higher percentages of PD1-expressing immune cells (cDC, CD56dimCD16+, CD8+, CD4+, CD19+) compared to Cluster 2.
Conclusions:
- Immunological distinctions correlate with BCR::ABL1 transcript type in CML patients.
- These immune differences may impact the number of active CML cells and influence molecular recurrence risk.
