Tracking leukemic residuals: dissecting the inverse relationship between CD26+ stem cells and extracellular BCR::ABL1 transcript in Chronic Myeloid Leukemia (CML)

Chronic myeloid leukemia (CML) persists due to leukemic stem cells, notably the CD26+ subset. We investigated correlations between circulating CD26+ leukemic stem cells (LSCs) and BCR::ABL1 transcripts in an extracellular vesicle-enriched secretome (EVES) from plasma samples of 44 CML patients. EVES were characterized and BCR::ABL1 quantified via digital PCR. We observed an inverse correlation between CD26+LSC counts and EVES BCR::ABL1 levels, especially in deep molecular responders (DMR). CD26+LSCs were elevated in patients in treatment-free remission (TFR), while EVES BCR::ABL1 levels were higher in those receiving therapy. These findings suggest distinct dynamics between LSC populations and vesicle-mediated transcript release, with potential implications for CML monitoring and prognosis. © 2025 The Author(s).