血浆循环中的miR-638、miR-6511b-5p、miR-3613-5p、miR-455-3p、miR-5787和miR-548a-3p作为急性髓系白血病患者异基因造血干细胞移植后免疫重建的非侵入性生物标志物。

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.

作者信息

Izadifard Marzieh, Ahmadvand Mohammad, Chahardouli Bahram, Vaezi Mohammad, Janbabai Ghasem, Seghatoleslami Ghazal, Bahrami Mehran, Yaghmaie Marjan, Barkhordar Maryam

机构信息

Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology, and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Transpl Immunol. 2025 Jun;91:102240. doi: 10.1016/j.trim.2025.102240. Epub 2025 May 8.

DOI:10.1016/j.trim.2025.102240

PMID:40347984

Abstract

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.

摘要

引言

异基因造血干细胞移植（allo-HSCT）是急性髓系白血病（AML）的一种可行治疗选择，尽管它存在包括免疫重建延迟和造血重建失败等风险。本研究旨在探讨循环miRNA水平作为移植后免疫重建生物标志物的潜力。

方法

本观察性研究于2020年至2023年在伊朗沙里亚蒂医院对接受来自HLA匹配同胞供体的allo-HSCT的初发非M3 AML患者进行。据此，通过十色多参数流式细胞术对移植前和移植后第30天采集的血样进行NK细胞、T细胞和B细胞的免疫表型分析。同时，使用定量逆转录聚合酶链反应（RT qPCR）对miR-638、miR-6511b-5p、miR-3613-5p、miR-455-3p、miR-5787和miR-548a-3p的血浆水平进行定量。

结果

miR-638、miR-3613-5p、miR-455-3p和miR-548a-3p的表达与CD4 T细胞、CD4/CD8 T细胞比值、CD3/16/56细胞和血小板计数呈正相关。miR-455-3p和miR-3613-5p表达升高与较高的CD3/16/56细胞相关（分别为P = 0.0475和P = 0.0325）。同样，miR-638上调与CD4 T细胞增加（P = 0.0112）和CD4/CD8 T细胞比值增加（P = 0.006）相关，而miR-548a-3p上调与CD4/CD8 T细胞比值增加（P = 0.0353）和血小板计数增加（P = 0.0191）相关。相反，miR-3613-5p和miR-6511b-5p与CD8 T细胞有显著负相关（分别为P = 0.03和P = 0.0246），而miR-5787与CD3/16/56细胞负相关（P = 0.025）。