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Phosphorylated ERK1/2 in CD4 T cells is associated with acute GVHD in allogeneic hematopoietic stem cell transplantation

発表形態:
原著論文
主要業績:
主要業績
単著・共著:
共著
発表年月:
2020年02月
DOI:
10.1182/bloodadvances.2019000343
会議属性:
指定なし
査読:
有り
リンク情報:

日本語フィールド

著者:
Hidekazu Itamura, Takero Shindo, Satoshi Yoshioka, Takayuki Ishikawa, Shinya Kimura
題名:
Phosphorylated ERK1/2 in CD4 T cells is associated with acute GVHD in allogeneic hematopoietic stem cell transplantation
発表情報:
Blood Adv 巻: 4 号: 4 ページ: 667-671
キーワード:
概要:
To diagnose graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is sometimes difficult. We showed previously that MEK inhibitors selectively suppress murine GVHD while retaining antiviral and antitumor immunity. Here, we asked whether the RAS/MEK/ERK pathway is activated in human allo-HSCT recipients with GVHD, and whether the phosphorylated ERK1/2 can be a biomarker of GVHD. Peripheral blood was sequentially collected from 20 allo-HSCT recipients: 1 bone marrow transplant, 7 peripheral blood stem cell transplants (PBSCT), and 12 cord blood transplants. Ten of the 20 allo-HSCT recipients developed GVHD, and phosphorylation of ERK1/2 in T and B cells was analyzed by flow cytometry. Occurrence of acute GVHD was associated with phosphorylation of ERK1/2 in CD4+ T cells at day 30 (P < .001), which was suppressed by ex vivo exposure to a MEK inhibitor trametinib at clinically achievable concentrations. In particular, ERK1/2 was phosphorylated preferentially in naive/central memory CD4+ T cells. Notably, phosphorylation of ERK1/2 fell as GVHD improved. These results suggest that phosphorylation status of ERK1/2 in peripheral blood CD4+ T cells may be a future biomarker for diagnosing human GVHD, and the potential efficacy of MEK inhibitors against human GVHD.
抄録:

英語フィールド

Author:
Hidekazu Itamura, Takero Shindo, Satoshi Yoshioka, Takayuki Ishikawa, Shinya Kimura
Title:
Phosphorylated ERK1/2 in CD4 T cells is associated with acute GVHD in allogeneic hematopoietic stem cell transplantation
Announcement information:
Blood Adv Vol: 4 Issue: 4 Page: 667-671
An abstract:
To diagnose graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is sometimes difficult. We showed previously that MEK inhibitors selectively suppress murine GVHD while retaining antiviral and antitumor immunity. Here, we asked whether the RAS/MEK/ERK pathway is activated in human allo-HSCT recipients with GVHD, and whether the phosphorylated ERK1/2 can be a biomarker of GVHD. Peripheral blood was sequentially collected from 20 allo-HSCT recipients: 1 bone marrow transplant, 7 peripheral blood stem cell transplants (PBSCT), and 12 cord blood transplants. Ten of the 20 allo-HSCT recipients developed GVHD, and phosphorylation of ERK1/2 in T and B cells was analyzed by flow cytometry. Occurrence of acute GVHD was associated with phosphorylation of ERK1/2 in CD4+ T cells at day 30 (P < .001), which was suppressed by ex vivo exposure to a MEK inhibitor trametinib at clinically achievable concentrations. In particular, ERK1/2 was phosphorylated preferentially in naive/central memory CD4+ T cells. Notably, phosphorylation of ERK1/2 fell as GVHD improved. These results suggest that phosphorylation status of ERK1/2 in peripheral blood CD4+ T cells may be a future biomarker for diagnosing human GVHD, and the potential efficacy of MEK inhibitors against human GVHD.


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