The PD1 Molecule May Contribute to Lower Treatment-Free Remission Rates in Patients with Chronic Myeloid Leukemia with the e13a2 Transcript

<b>Background/Objectives</b>: Chronic myeloid leukemia (CML) is characterized by the presence of the <i>BCR::ABL1</i> fusion gene, most commonly in the e14a2 or e13a2 variants. Studies show that the transcript type in CML may be important for achieving treatment-free remission (TFR). This study aimed to immunologically characterize CML patients with e13a2 and e14a2 transcripts to search for differences that may contribute to achieving remission in patients after therapy withdrawal. <b>Methods</b>: Using multicolor flow cytometry, we analyzed the differences in the immune system at the time of imatinib discontinuation and the early stage of TFR in fifty-one CML patients with different transcripts. RQ-PCR and ddPCR were used to monitor the dynamics of <i>BCR::ABL1</i> transcript changes. The patients were grouped using principal component analysis (PCA) based on the percentage of detected immune cells that were classified as populations consistently selected by the MCFS-ID algorithm from randomly selected data. <b>Results</b>: PCA separated CML patients into two groups defined by k-means clustering, indicating significant heterogeneity within the studied population. We found a significant association between Cluster metrics (Cluster 1 and 2) and <i>BCR::ABL1</i> transcript types (e13a2 or e14a2) (<i>p</i> = 0.003, 95% CI: 0.026-0.595, OR = 0.14, Fisher test). The e13a2 transcript was less frequent in Cluster 2 than in Cluster 1, while e14a2 was more common in Cluster 2. Additionally, patients grouped into Cluster 1 had significantly higher percentages of the PD1 expressing populations cDC PD1⁺, CD56^dimCD16⁺PD1⁺, CD8⁺PD1⁺, CD4⁺PD1⁺, and CD19⁺PD1⁺, as identified by the MCFS-ID algorithm, compared to patients in Cluster 2. <b>Conclusions</b>: Our results suggest that immunological differences may be related to the <i>BCR::ABL1</i> transcript type, which could affect the number of active CML cells represented by the <i>BCR::ABL1</i> transcript amount and thus may determine molecular recurrence.