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

Phosphorylated ERK1/2 in CD4 T cells is associated with acute GVHD in allogeneic hematopoietic stem cell transplantation
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DOI:
10.1182/bloodadvances.2019000343
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发表时间:
2020-02-25
期刊:
影响因子:
7.5
通讯作者:
Kimura, Shinya
Kimura, Shinya
中科院分区:
医学1区
文献类型:
--
作者:
Itamura, Hidekazu;Shindo, Takero;Kimura, Shinya

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异基因造血干细胞移植(allo-HSCT)后移植物抗宿主病(GVHD)的诊断有时很困难。我们先前已经证明,MEK抑制剂选择性地抑制小鼠GVHD,同时保留抗病毒和抗肿瘤免疫。在此,我们探讨了RAS/MEK/ERK通路是否在GVHD患者的allo-HSCT受者中被激活,以及磷酸化的ERK1/2是否可以作为GVHD的生物标志物。先后采集20例allo-HSCT患者的外周血,其中骨髓移植1例,外周血干细胞移植7例,脐血移植12例。20例allo-HSCT受者中有10例发生移植物抗宿主病(GVHD),用流式细胞仪检测T、B细胞ERK1/2的磷酸化情况。急性移植物抗宿主病的发生与第30天CD41T细胞ERK1/2的磷酸化有关(P
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 CD41 T cells at day 30 (P