Transcription profiling of human leukocytes from peripheral blood stem cell transplant patients to investigate acute graft versus host disease aGVHD
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ABSTRACT: Allogeneic peripheral blood stem cell transplantation (PBSCT) is indicated for the treatment of high-risk hematological malignancies, and in some cases is a cancer cure. A major complication associated with PBSCT (affecting approximately half of recipients) is acute graft-versus-host disease (aGVHD). In aGVHD, alloreactive donor T cells becoming activated by host dendritic cells (DC) in response to pro-inflammatory cytokines released during the conditioning regimen. The result is donor-derived CD4+ T helper-type 1 (Th1) cells maturing and subsequently imposing cytolytic effector responses on host tissues, resulting in multi-organ damage. Despite this well-defined pathophysiological mechanism, there are no definitive markers for predicting aGVHD development or progression to clinically advanced stages. In the current study, we enrolled 8 PBSCT recipients in an IRB-approved study and collected peripheral blood at the time to engraftment. Of these, four patients developed aGVHD within 5-10 days post transplant. The remaining four patients were aGVHD-free. Using total RNA collected from whole blood leukocytes, we analyzed each recipientâs gene expression profile on Affymetrix GeneChip Human Genome U133 Plus 2.0 microarrays. Experiment Overall Design: Samples 1-4 are control patients; 5-8 are aGVHD patients. Peripheral blood was collected at engraftment and used for microarray analysis. In analysing the data, the type of transplant (MUD, related) was used as a covariate to assess if there were significant changes in gene expression between the control (1-4) and aGVHD (5-8) groups, based on a 10% FDR with a pooled error estimate.
ORGANISM(S): Homo sapiens
SUBMITTER: Matthew Buzzeo
PROVIDER: E-GEOD-7510 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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