期刊
BLOOD ADVANCES
卷 4, 期 4, 页码 667-671出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/bloodadvances.2019000343
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资金
- MEXT KAKENHI [26461451]
- Takeda Science Foundation
- SENSHIN Medical Research Foundation
- Kobayashi Cancer Research Foundation
- Bristol-Myers Squibb Foundation
- Kanae Foundation for the Promotion of Medical Science
- Grants-in-Aid for Scientific Research [26461451] Funding Source: KAKEN
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<.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 CD41 T cells. Notably, phosphorylation of ERK1/2 fell as GVHD improved. These results suggest that phosphorylation status of ERK1/2 in peripheral blood CD41 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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