Plasma-circulating miR-638, miR-6511b-5p, miR-3613-5p, miR-455-3p, miR-5787, and miR-548a-3p as noninvasive biomarkers of immune reconstitution post-allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients.

INTRODUCTION

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a viable treatment option for acute myeloid leukemia (AML), though it carries risks including delayed immune reconstitution and hematopoietic reconstitution failure. This study aimed to explore the potential of circulating miRNA levels as biomarkers for post-transplant immune reconstitution.

METHODS

This observational study was carried out on de novo non-M3 AML patients receiving allo-HSCT from HLA-matched sibling donors at Shariati Hospital, Iran in 2020-2023. Accordingly, the immunophenotype of NK cells, T cells, and B cells was determined by ten-color multiparameter flow cytometry on blood samples collected pre-transplantation and at day +30 post-transplantation. Concurrently, plasma levels of miR-638, miR-6511b-5p, miR-3613-5p, miR-455-3p, miR-5787, and miR-548a-3p were quantified using quantitative reverse transcription-polymerase chain reaction (RT qPCR).

RESULTS

The expression of miR-638, miR-3613-5p, miR-455-3p, and miR-548a-3p positively correlated with CD4+ T cells, CD4+/CD8+ T cell ratio, CD3-/16+/56- cells, and platelet count. Elevated miR-455-3p and miR-3613-5p expressions were associated with higher CD3-/16+/56- cells (P = 0.0475 and P = 0.0325, respectively). Similarly, miR-638 upregulation correlated with increases in CD4+ T cells (P = 0.0112) and the CD4+/CD8+ T cell ratio (P = 0.006), while miR-548a-3p upregulation was associated with increases in the CD4+/CD8+ T cell ratio (P = 0.0353) and platelet count (P = 0.0191). Conversely, miR-3613-5p and miR-6511b-5p had considerable negative correlations with CD8+ T cells (P = 0.03 and P = 0.0246, respectively), whereas miR-5787 negatively correlated with CD3+/16-/56+ cells (P = 0.025).

CONCLUSION

Our findings suggest that differentiation of cell subpopulations is regulated by specific miRNAs. Furthermore, miRNA-based strategies may be developed for immunotherapeutic treatments of AML.