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Phosphorylated ERK1/2 in CD4 T cells is associated with acute GVHD in allogeneic hematopoietic stem cell transplantation
| Content Provider | Scilit |
|---|---|
| Author | Itamura, Hidekazu Shindo, Takero Yoshioka, Satoshi Ishikawa, Takayuki Kimura, Shinya |
| Copyright Year | 2020 |
| Description | 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042985/pdf |
| Ending Page | 671 |
| Page Count | 5 |
| Starting Page | 667 |
| DOI | 10.1182/bloodadvances.2019000343 |
| Journal | Blood advances |
| Issue Number | 4 |
| Volume Number | 4 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2020-02-25 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Hematopoietic Bone Marrow Antiviral Phosphorylation Erk1/2 Stem Transplantation Gvhd Cd4 Allo Hsct Journal: Blood advances (Vol- 73, Issue- 4) |
| Content Type | Text |
| Resource Type | Article |
