ArticleLeukemia2012
Spleen tyrosine kinase (Syk) is a potent target for GvHD prevention at different cellular levels.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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
26 citing papers in PubMed, 45 citations in OpenAlex.
- Graft-Versus-Host Disease Mouse Models: A Clinical-Translational Perspective.Methods in molecular biology (Clifton, N.J.) · 2025Review
- ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease.Nature communications · 2024Article
- The ocular graft-versus-host disease: the path from current knowledge to future managements.Eye (London, England) · 2023Review
- A Phase I Trial of SYK Inhibition with Fostamatinib in the Prevention and Treatment of Chronic Graft-Versus-Host Disease.Transplantation and cellular therapy · 2023Article
- Dual inhibition of the MEK/ERK and PI3K/AKT pathways prevents pulmonary GVHD suppressing perivenulitis and bronchiolitis.Blood advances · 2023Article
- Recent advances in graft-versus-host disease.Faculty reviews · 2023Review
- Article
- National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2020 Etiology and Prevention Working Group Report.Transplantation and cellular therapy · 2021Review
- The Pathophysiology and Treatment of Graft-Frontiers in immunology · 2021Review
- Kinase Inhibition as Treatment for Acute and Chronic Graft-Frontiers in immunology · 2021Review
- Immunopathology and biology-based treatment of steroid-refractory graft-versus-host disease.Blood · 2020Review
- Developing role of B cells in the pathogenesis and treatment of chronic GVHD.British journal of haematology · 2019Review
- SYK inhibitor entospletinib prevents ocular and skin GVHD in mice.JCI insight · 2018Article
- The search for drug-targetable diagnostic, prognostic and predictive biomarkers in chronic graft-versus-host disease.Expert review of clinical immunology · 2018Review
- New and emerging therapies for acute and chronic graftTherapeutic advances in hematology · 2018Review
- The kinase inhibitors R406 and GS-9973 impair T cell functions and macrophage-mediated anti-tumor activity of rituximab in chronic lymphocytic leukemia patients.Cancer immunology, immunotherapy : CII · 2017Article
- Article
- Therapeutic targets and emerging treatment options in gastrointestinal acute graft-versus-host disease.Expert opinion on orphan drugs · 2016Article
- The Role of Purine Metabolites as DAMPs in Acute Graft-versus-Host Disease.Frontiers in immunology · 2016Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute graft-versus-host disease (GvHD) limits the applicability of allogeneic hematopoietic cell transplantation for the treatment of leukemia. GvHD occurs as a consequence of multiple activating events in antigen-presenting cells (APCs) and T cells (Tcs). Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase involved in multiple signaling events of immune cells. Therefore, we hypothesized that Syk may be a promising target to inhibit GvHD, which involves activation of different immune cell populations. In vivo expansion of luciferase(+) donor Tcs in mice developing GvHD was reduced by treatment with the Syk inhibitor Fostamatinib, which led to increased survival and reduced histologically confirmed GvHD severity. Importantly, in vivo and in vitro cytotoxicity against leukemia target cells and anti-murine cytomegalovirus immune responses were not impacted by Fostamatinib. In APCs Syk inhibition reduced the expression of costimulatory molecules and disrupted cytoskeletal organization with consecutive APC migratory defects in vitro and in vivo while phagocytic activity remained intact. On the basis of these immunomodulatory effects on different cell populations, we conclude that Syk targeting in alloantigen-activated Tcs and APCs with pharmacologic inhibitors, already applied successfully in anti-lymphoma therapy, has clinical potential to reduce GvHD, especially as anti-leukemia and anti-viral immunity were preserved.
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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.