Unravelling a clinical role of peripheral blood leukemia stem cells at diagnosis in chronic myeloid leukemia patients: Final results of prospective FLOWERS study

Cancer. 2025 Oct 15;131(20):e70122. doi: 10.1002/cncr.70122.

Abstract

Background: The authors previously demonstrated that in peripheral blood (PB) of chronic myeloid leukemia (CML), patients' leukemia stem cells (LSCs) CD26+ are detectable by flow cytometry at diagnosis, during tyrosine kinase inhibitor (TKI) therapy, and during treatment-free remission.

Methods: This study presents results of a prospective multicenter study including 242 newly diagnosed CML patients monitored for PB CD26+ leukemic stem cells (LSCs) quantification from diagnosis up to 24 months of TKI treatment.

Results: The bulk of CD26+ LSCs at diagnosis varied between patients with a median value of 7.14 cells/µL. During TKI treatment, it has been observed their consistent and rapid reduction without statistical differences according to type of first-line TKI. Instead, a significant correlation between a low amount of CD26+ LSCs at diagnosis and an optimal molecular response at 3, 12, and 24 months was documented (p = .03, p = .004, and p = .009, respectively). Three tertiles of CD26+ LSCs correlating to molecular response were identified: <3.21 cells/µL; between 3.21 and 19.21 cells/µL; and >19.21 cells/µL. The incidence of patients with optimal response was higher in the first CD26+ LSCs tertile respect to the third one (p = .027, p = .015, and p = .079, respectively) at all time points (3, 12 and 24 months).

Conclusions: This study demonstrated a correlation between the amount of CD26+ LSCs at diagnosis and the molecular response, suggesting that the number of CD26+ LSCs at diagnosis could represent an additional tool for predicting TKI response.

Keywords: CD26; chronic myeloid leukemia; flow cytometry; leukemia stem cells; tyrosine kinase inhibitors.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Dipeptidyl Peptidase 4 / blood
  • Dipeptidyl Peptidase 4 / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / pathology
  • Male
  • Middle Aged
  • Neoplastic Stem Cells* / drug effects
  • Neoplastic Stem Cells* / metabolism
  • Neoplastic Stem Cells* / pathology
  • Prospective Studies
  • Protein Kinase Inhibitors* / therapeutic use
  • Young Adult

Substances

  • Protein Kinase Inhibitors
  • Dipeptidyl Peptidase 4
  • DPP4 protein, human