ArticleScience translational medicine2015
Transcriptome analysis of GVHD reveals aurora kinase A as a targetable pathway for disease prevention.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Meta-Analysis of Genome-Wide Association and Gene Expression Studies Implicates Donor T Cell Function and Cytokine Pathways in Acute GvHD.Frontiers in immunology · 2020Pooled it
- Trial
- Concerted changes in the pediatric single-cell intestinal ecosystem before and after anti-TNF blockade.eLife · 2026Article
- Targeting Aurora kinase A to prevent GVHD and relapse after myeloablative allogeneic hematopoietic cell transplantation.Blood advances · 2026Article
- Article
- Whole-Blood Longitudinal Molecular Profiling Maps the Road of Graft Versus Host Disease (GVHD).Cancers · 2025Article
- Organ-specific microenvironments drive divergent T cell evolution in acute graft-versus-host disease.Science translational medicine · 2025Article
- Genetic and pharmaceutical targeting of HIF1α allows combo-immunotherapy to boost graft vs. leukemia without exacerbation graft vs. host disease.Cell reports. Medicine · 2023Article
- Transcriptome analysis in acute gastrointestinal graft-Haematologica · 2023Article
- Notch signaling drives intestinal graft-versus-host disease in mice and nonhuman primates.Science translational medicine · 2023Article
- Post-transplant cyclophosphamide prevents xenogeneic graft-versus-host disease while depleting proliferating regulatory T cells.iScience · 2023Article
- Milestones in acute GVHD pathophysiology.Frontiers in immunology · 2022Review
- Metabolic Reprogramming of Alloreactive T Cells Through TCR/MYC/mTORC1/E2F6 Signaling in aGvHD Patients.Frontiers in immunology · 2022Article
- Insights from integrating clinical and preclinical studies advance understanding of graft-versus-host disease.The Journal of clinical investigation · 2021Review
- Pacritinib Combined with Sirolimus and Low-Dose Tacrolimus for GVHD Prevention after Allogeneic Hematopoietic Cell Transplantation: Preclinical and Phase I Trial Results.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Current Concepts and Advances in Graft-Versus-Host Disease Immunology.Annual review of immunology · 2021Article
- RNA-seq of human T cells after hematopoietic stem cell transplantation identifiesScience translational medicine · 2021Article
- Post-haematopoietic cell transplantation outcomes: why ST2 became a 'golden nugget' biomarker.British journal of haematology · 2021Review
- Spatiotemporal single-cell profiling reveals that invasive and tissue-resident memory donor CD8Science translational medicine · 2021Article
- Kinase Inhibition as Treatment for Acute and Chronic Graft-Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
Graft-versus-host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of nonhuman primate (NHP) T cells during acute GVHD. Utilizing microarray technology, we measured the expression profiles of CD3(+) T cells from five cohorts: allogeneic transplant recipients receiving (i) no immunoprophylaxis (No Rx), (ii) sirolimus monotherapy (Siro), (iii) tacrolimus-methotrexate (Tac-Mtx), as well as (iv) autologous transplant recipients (Auto) and (v) healthy controls (HC). This comparison allowed us to identify transcriptomic signatures specific for alloreactive T cells and determine the impact of both mTOR (mechanistic target of rapamycin) and calcineurin inhibition on GVHD. We found that the transcriptional profile of unprophylaxed GVHD was characterized by significant perturbation of pathways regulating T cell proliferation, effector function, and cytokine synthesis. Within these pathways, we discovered potentially druggable targets not previously implicated in GVHD, prominently including aurora kinase A (AURKA). Utilizing a murine GVHD model, we demonstrated that pharmacologic inhibition of AURKA could improve survival. Moreover, we found enrichment of AURKA transcripts both in allo-proliferating T cells and in sorted T cells from patients with clinical GVHD. These data provide a comprehensive elucidation of the T cell transcriptome in primate acute GVHD and suggest that AURKA should be considered a target for preventing GVHD, which, given the many available AURKA inhibitors in clinical development, could be quickly deployed for the prevention of GVHD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.