Toll-like receptor genetic variations in bone marrow transplantation

Kaori Uchino, Shohei Mizuno, Aiko Sato-Otsubo, Yasuhito Nannya, Motonori Mizutani, Tomohiro Horio, Ichiro Hanamura, J. Luis Espinoza, Makoto Onizuka, Koichi Kashiwase, Yasuo Morishima, Takahiro Fukuda, Yoshihisa Kodera, Noriko Doki, Koichi Miyamura, Takehiko Mori, Seishi Ogawa, Akiyoshi Takami

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The Toll-like receptor family mediates the innate immune system through recognizing the molecular patterns of microorganisms and self-components and leading the synthesis of the inflammatory mediators. We retrospectively examined whether or not genetic variations in toll-like receptor 1 (rs5743551, -7202GQ > A), toll-like receptor 2 (rs7656411, 22215G > T), and toll-like receptor 4 (rs11536889, +3725G > C) affected transplant outcomes in a cohort of 365 patients who underwent unrelated HLA-matched bone marrow transplantation (for hematologic malignancies through the Japan Marrow Donor Program. Only donor toll-like receptor 4 variation significantly improved the survival outcomes. A multivariate analysis showed that the donor toll-like receptor 4 +3725G/G genotype was significantly associated with a better 5-year progression-free survival and a lower 5-year transplant-related mortality than other variations. Furthermore, the donor toll-like receptor 4 +3725G/G genotype was associated with a significantly lower incidence of fatal infections than other variations. The validation study of 502 patients confirmed that the donor tolllike receptor 4 +3725G/G genotype was associated with better survival outcomes. Toll-like receptor4 genotyping in transplant donors may therefore be a useful tool for optimizing donor selection and evaluating pretransplantation risks.

Original languageEnglish
Pages (from-to)45670-45686
Number of pages17
JournalOncotarget
Volume8
Issue number28
DOIs
Publication statusPublished - 2017

Fingerprint

Toll-Like Receptor 4
Toll-Like Receptors
Bone Marrow Transplantation
Genotype
Tissue Donors
Toll-Like Receptor 1
Transplants
Toll-Like Receptor 2
Donor Selection
Survival
Validation Studies
Hematologic Neoplasms
Disease-Free Survival
Immune System
Japan
Multivariate Analysis
Bone Marrow
Mortality
Incidence
Infection

Keywords

  • Bone marrow transplantation
  • Single nucleotide variation
  • Toll-like receptor
  • Unrelated donor

ASJC Scopus subject areas

  • Oncology

Cite this

Uchino, K., Mizuno, S., Sato-Otsubo, A., Nannya, Y., Mizutani, M., Horio, T., ... Takami, A. (2017). Toll-like receptor genetic variations in bone marrow transplantation. Oncotarget, 8(28), 45670-45686. https://doi.org/10.18632/oncotarget.17315

Toll-like receptor genetic variations in bone marrow transplantation. / Uchino, Kaori; Mizuno, Shohei; Sato-Otsubo, Aiko; Nannya, Yasuhito; Mizutani, Motonori; Horio, Tomohiro; Hanamura, Ichiro; Espinoza, J. Luis; Onizuka, Makoto; Kashiwase, Koichi; Morishima, Yasuo; Fukuda, Takahiro; Kodera, Yoshihisa; Doki, Noriko; Miyamura, Koichi; Mori, Takehiko; Ogawa, Seishi; Takami, Akiyoshi.

In: Oncotarget, Vol. 8, No. 28, 2017, p. 45670-45686.

Research output: Contribution to journalArticle

Uchino, K, Mizuno, S, Sato-Otsubo, A, Nannya, Y, Mizutani, M, Horio, T, Hanamura, I, Espinoza, JL, Onizuka, M, Kashiwase, K, Morishima, Y, Fukuda, T, Kodera, Y, Doki, N, Miyamura, K, Mori, T, Ogawa, S & Takami, A 2017, 'Toll-like receptor genetic variations in bone marrow transplantation', Oncotarget, vol. 8, no. 28, pp. 45670-45686. https://doi.org/10.18632/oncotarget.17315
Uchino K, Mizuno S, Sato-Otsubo A, Nannya Y, Mizutani M, Horio T et al. Toll-like receptor genetic variations in bone marrow transplantation. Oncotarget. 2017;8(28):45670-45686. https://doi.org/10.18632/oncotarget.17315
Uchino, Kaori ; Mizuno, Shohei ; Sato-Otsubo, Aiko ; Nannya, Yasuhito ; Mizutani, Motonori ; Horio, Tomohiro ; Hanamura, Ichiro ; Espinoza, J. Luis ; Onizuka, Makoto ; Kashiwase, Koichi ; Morishima, Yasuo ; Fukuda, Takahiro ; Kodera, Yoshihisa ; Doki, Noriko ; Miyamura, Koichi ; Mori, Takehiko ; Ogawa, Seishi ; Takami, Akiyoshi. / Toll-like receptor genetic variations in bone marrow transplantation. In: Oncotarget. 2017 ; Vol. 8, No. 28. pp. 45670-45686.
@article{31f6f7afef45455b912bd0b4c997d6c7,
title = "Toll-like receptor genetic variations in bone marrow transplantation",
abstract = "The Toll-like receptor family mediates the innate immune system through recognizing the molecular patterns of microorganisms and self-components and leading the synthesis of the inflammatory mediators. We retrospectively examined whether or not genetic variations in toll-like receptor 1 (rs5743551, -7202GQ > A), toll-like receptor 2 (rs7656411, 22215G > T), and toll-like receptor 4 (rs11536889, +3725G > C) affected transplant outcomes in a cohort of 365 patients who underwent unrelated HLA-matched bone marrow transplantation (for hematologic malignancies through the Japan Marrow Donor Program. Only donor toll-like receptor 4 variation significantly improved the survival outcomes. A multivariate analysis showed that the donor toll-like receptor 4 +3725G/G genotype was significantly associated with a better 5-year progression-free survival and a lower 5-year transplant-related mortality than other variations. Furthermore, the donor toll-like receptor 4 +3725G/G genotype was associated with a significantly lower incidence of fatal infections than other variations. The validation study of 502 patients confirmed that the donor tolllike receptor 4 +3725G/G genotype was associated with better survival outcomes. Toll-like receptor4 genotyping in transplant donors may therefore be a useful tool for optimizing donor selection and evaluating pretransplantation risks.",
keywords = "Bone marrow transplantation, Single nucleotide variation, Toll-like receptor, Unrelated donor",
author = "Kaori Uchino and Shohei Mizuno and Aiko Sato-Otsubo and Yasuhito Nannya and Motonori Mizutani and Tomohiro Horio and Ichiro Hanamura and Espinoza, {J. Luis} and Makoto Onizuka and Koichi Kashiwase and Yasuo Morishima and Takahiro Fukuda and Yoshihisa Kodera and Noriko Doki and Koichi Miyamura and Takehiko Mori and Seishi Ogawa and Akiyoshi Takami",
year = "2017",
doi = "10.18632/oncotarget.17315",
language = "English",
volume = "8",
pages = "45670--45686",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "28",

}

TY - JOUR

T1 - Toll-like receptor genetic variations in bone marrow transplantation

AU - Uchino, Kaori

AU - Mizuno, Shohei

AU - Sato-Otsubo, Aiko

AU - Nannya, Yasuhito

AU - Mizutani, Motonori

AU - Horio, Tomohiro

AU - Hanamura, Ichiro

AU - Espinoza, J. Luis

AU - Onizuka, Makoto

AU - Kashiwase, Koichi

AU - Morishima, Yasuo

AU - Fukuda, Takahiro

AU - Kodera, Yoshihisa

AU - Doki, Noriko

AU - Miyamura, Koichi

AU - Mori, Takehiko

AU - Ogawa, Seishi

AU - Takami, Akiyoshi

PY - 2017

Y1 - 2017

N2 - The Toll-like receptor family mediates the innate immune system through recognizing the molecular patterns of microorganisms and self-components and leading the synthesis of the inflammatory mediators. We retrospectively examined whether or not genetic variations in toll-like receptor 1 (rs5743551, -7202GQ > A), toll-like receptor 2 (rs7656411, 22215G > T), and toll-like receptor 4 (rs11536889, +3725G > C) affected transplant outcomes in a cohort of 365 patients who underwent unrelated HLA-matched bone marrow transplantation (for hematologic malignancies through the Japan Marrow Donor Program. Only donor toll-like receptor 4 variation significantly improved the survival outcomes. A multivariate analysis showed that the donor toll-like receptor 4 +3725G/G genotype was significantly associated with a better 5-year progression-free survival and a lower 5-year transplant-related mortality than other variations. Furthermore, the donor toll-like receptor 4 +3725G/G genotype was associated with a significantly lower incidence of fatal infections than other variations. The validation study of 502 patients confirmed that the donor tolllike receptor 4 +3725G/G genotype was associated with better survival outcomes. Toll-like receptor4 genotyping in transplant donors may therefore be a useful tool for optimizing donor selection and evaluating pretransplantation risks.

AB - The Toll-like receptor family mediates the innate immune system through recognizing the molecular patterns of microorganisms and self-components and leading the synthesis of the inflammatory mediators. We retrospectively examined whether or not genetic variations in toll-like receptor 1 (rs5743551, -7202GQ > A), toll-like receptor 2 (rs7656411, 22215G > T), and toll-like receptor 4 (rs11536889, +3725G > C) affected transplant outcomes in a cohort of 365 patients who underwent unrelated HLA-matched bone marrow transplantation (for hematologic malignancies through the Japan Marrow Donor Program. Only donor toll-like receptor 4 variation significantly improved the survival outcomes. A multivariate analysis showed that the donor toll-like receptor 4 +3725G/G genotype was significantly associated with a better 5-year progression-free survival and a lower 5-year transplant-related mortality than other variations. Furthermore, the donor toll-like receptor 4 +3725G/G genotype was associated with a significantly lower incidence of fatal infections than other variations. The validation study of 502 patients confirmed that the donor tolllike receptor 4 +3725G/G genotype was associated with better survival outcomes. Toll-like receptor4 genotyping in transplant donors may therefore be a useful tool for optimizing donor selection and evaluating pretransplantation risks.

KW - Bone marrow transplantation

KW - Single nucleotide variation

KW - Toll-like receptor

KW - Unrelated donor

UR - http://www.scopus.com/inward/record.url?scp=85022226779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85022226779&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.17315

DO - 10.18632/oncotarget.17315

M3 - Article

VL - 8

SP - 45670

EP - 45686

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 28

ER -