Toll-like receptor 1 variation increases the risk of transplant-related mortality in hematologic malignancies

Uchino, Kaori; Mizuno, Shohei; Mizutani, Motonori; Horio, Tomohiro; Hanamura, Ichiro; Espinoza, J. Luis; Matsuo, Keitaro; Onizuka, Makoto; Kashiwase, Koichi; Morishima, Yasuo; Fukuda, Takahiro; Kodera, Yoshihisa; Doki, Noriko; Miyamura, Koichi; Mori, Takehiko; Takami, Akiyoshi

doi:10.1016/j.trim.2016.06.002

Cited by 3 publications

(2 citation statements)

References 28 publications

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“…Previous studies [18][19][20][21] have suggested that the TLR -signaling pathway plays important roles in the anti-microbial immunity and GVHD after allogeneic SCT. TLR genes have several functional single-nucleotide polymorphisms (SNPs), which have been shown to be associated with the survival outcomes after allogeneic SCT in our recent reports [22,23]. TLRs are present not only on the cell surface but also inside the cell, and such intracellular TLRs are translocated from the ER to endolysosomes, which are critically regulated by UNC-93 homolog B1 (UNC93B1), an ER protein with 12 membrane-spanning domains [24].…”

Section: Introductionmentioning

confidence: 99%

Donor UNC-93 Homolog B1 genetic polymorphism predicts survival outcomes after unrelated bone marrow transplantation

et al. 2021

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UNC-93 homolog B1 (UNC93B1) is a key regulator of toll-like receptors (TLRs), pattern recognition receptors that sense invading pathogens and manage the innate immune response and deliver them from the endoplasmic reticulum to their respective endosomal signaling compartments. Several types of TLRs are known to contribute to the inflammatory process after allogeneic hematopoietic stem cell transplantation (SCT), so UNC93B1 might play integral roles there. We investigated the influence of the UNC93B1 single-nucleotide polymorphism (SNP) rs308328 (T>C) on transplant outcomes in a cohort of 237 patients undergoing unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. The donor UNC93B1 C/C genotype was associated with a better 3-year overall survival than the donor UNC93B1 C/T or T/T genotype. An analysis of the UNC93B1 rs308328 genotype may therefore be useful for selecting the donor, estimating the prognosis, and creating therapeutic strategies after allogeneic SCT.

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Section: Introductionmentioning

confidence: 99%

Donor UNC-93 Homolog B1 genetic polymorphism predicts survival outcomes after unrelated bone marrow transplantation

et al. 2021

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“…One important single nucleotide polymorphism (SNP) in the promoter region of the HO-1 gene, rs2071746 (-413A>T), is functional, and the major A allele is reported to be associated with higher expression of HO-1 than the minor T allele [18,19]. There is growing evidence to support that non-human leukocyte antigen (HLA) genetic polymorphism represents a significant determinant of outcomes after allo-HSCT [20][21][22][23][24][25][26]. These findings prompted us to investigate the impact of the rs2071746 SNP in the HO-1 gene on the clinical outcomes of patients undergoing allogeneic bone marrow transplantation (BMT), using an HLA allele-matched, unrelated donor through the Japan Marrow Donor Program (JMDP).…”

Section: Introductionmentioning

confidence: 99%

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

Horio

Morishita

Mizuno

et al. 2020

Cancers

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Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>T) that is functional, and the A allele has been reported to be associated with higher HO-1 expression levels than the T allele. We investigated the influence of the HO-1 rs2071746 SNP on the transplant outcomes in 593 patients with hematological malignancies undergoing unrelated, human leukocyte antigen (HLA)-matched, T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. In patients with high-risk diseases, the donor A/A or A/T genotype was associated with better 5 year overall survival (35% vs. 25%; p = 0.03) and 5 year disease-free survival (35% vs. 22%; p = 0.0072), compared to the donor T/T genotype. These effects were not observed in patients with low-risk diseases. The current findings therefore indicate that HO-1 rs2071746 genotyping could be useful for selecting donors and tailoring transplant strategies for patients with high-risk hematologic malignancies.

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The recipient CCR5 variation predicts survival outcomes after bone marrow transplantation

Horio

Mizuno

Uchino

et al. 2017

Transplant Immunology

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Toll-like receptor 1 variation increases the risk of transplant-related mortality in hematologic malignancies

Cited by 3 publications

References 28 publications

Donor UNC-93 Homolog B1 genetic polymorphism predicts survival outcomes after unrelated bone marrow transplantation

Donor UNC-93 Homolog B1 genetic polymorphism predicts survival outcomes after unrelated bone marrow transplantation

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

The recipient CCR5 variation predicts survival outcomes after bone marrow transplantation

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