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Background <p>Alloreactive T cells mediate graft-versus-leukemia (GvL) reactions and acute graft-versus-host disease (aGvHD) in AML patients following allogeneic hematopoietic stem cell transplantation.</p> Methods <p>To investigate biomarkers that identify alloreactive T cells associated with either beneficial GvL or detrimental aGvHD, we collected graft samples and two post-transplant follow-up blood samples (day 30 and day 100) of ten AML patients undergoing hematopoietic stem cell transplantation and profiled over 777,000 CD45<sup>+</sup> leukocytes in total by combinatorial barcoding-based mega-scale single-cell RNA sequencing.</p> Results <p>Using immune receptor sequences as intrinsic clonal barcodes, we observed that especially CD8<sup>+</sup> graft-derived T cells persisted and displayed enhanced proliferation, clonal expansion, and likely alloreactivity. Notably, patient-derived peripheral leukocytes that survived the conditioning, as identified by sex-chromosome-related genes, were primarily CD4<sup>+</sup> T helper cells. MDGA1 expression on T cells and NK cells emerged as a novel biomarker potentially associated with aGvHD. Additionally, we observed a significant deficiency of ADGRG1 expression, a marker of alloreactive cytotoxic T cells, by αβ and γδ T cells from relapsed patients.</p> Conclusions <p>In conclusion, mega-scale single-cell monitoring of graft and hematopoietic immune cell reconstitution allowed us to demonstrate that MDGA1 and ADGRG1 may function as complementary biomarkers expressed by distinct circulating T cells that are associated with divergent outcomes in AML patients, enabling precise risk stratification of alloHSCT outcomes and presenting potential therapeutic targets.</p> Graphical Abstract <p></p>

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Mega-scale single-cell profiling reveals novel biomarkers associated with acute GvHD after allogeneic hematopoietic stem cell transplantation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月1日

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  • Zheng Song,
  • Evgeny Klyuchnikov,
  • Anita Badbaran,
  • Likai Tan,
  • Regine J. Dress,
  • Emilia Czajkowski,
  • Simeon Weßler,
  • Radwan Massoud,
  • Christine Wolschke,
  • Anja Schimrock,
  • Yu Zhang,
  • Cedric Ly,
  • Nico Gagelmann,
  • Kristin Rathje,
  • Boris Fehse,
  • Stefan Bonn,
  • Sarina Ravens,
  • Nicola Gagliani,
  • Christian F. Krebs,
  • Ulf Panzer,
  • Francis Ayuk,
  • Nicolaus Kröger,
  • Immo Prinz

摘要

Background

Alloreactive T cells mediate graft-versus-leukemia (GvL) reactions and acute graft-versus-host disease (aGvHD) in AML patients following allogeneic hematopoietic stem cell transplantation.

Methods

To investigate biomarkers that identify alloreactive T cells associated with either beneficial GvL or detrimental aGvHD, we collected graft samples and two post-transplant follow-up blood samples (day 30 and day 100) of ten AML patients undergoing hematopoietic stem cell transplantation and profiled over 777,000 CD45+ leukocytes in total by combinatorial barcoding-based mega-scale single-cell RNA sequencing.

Results

Using immune receptor sequences as intrinsic clonal barcodes, we observed that especially CD8+ graft-derived T cells persisted and displayed enhanced proliferation, clonal expansion, and likely alloreactivity. Notably, patient-derived peripheral leukocytes that survived the conditioning, as identified by sex-chromosome-related genes, were primarily CD4+ T helper cells. MDGA1 expression on T cells and NK cells emerged as a novel biomarker potentially associated with aGvHD. Additionally, we observed a significant deficiency of ADGRG1 expression, a marker of alloreactive cytotoxic T cells, by αβ and γδ T cells from relapsed patients.

Conclusions

In conclusion, mega-scale single-cell monitoring of graft and hematopoietic immune cell reconstitution allowed us to demonstrate that MDGA1 and ADGRG1 may function as complementary biomarkers expressed by distinct circulating T cells that are associated with divergent outcomes in AML patients, enabling precise risk stratification of alloHSCT outcomes and presenting potential therapeutic targets.

Graphical Abstract