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- W2668879080 abstract "Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder originating from hematopoietic stem cells and is a life-threating disease characterized by intravascular hemolysis, bone marrow (BM) failure, and venous thrombosis. The etiology of PNH is a somatic mutation in the phosphatidylinositol glycan class A gene (PIG-A) on the X chromosome, which blocks synthesis of the glycolipid moiety and causes deficiency in GPI-anchored proteins. PNH is closely related to aplastic anemia, in which T cells mediate destruction of BM. To identify aberrant molecular mechanisms involved in immune targeting of hematopoietic stem cells in BM, we applied RNA-seq to examine the transcriptome of T cell subsets (CD4+ naive, CD4+ memory, CD8+ naive, and CD8+ memory) from PNH patients and healthy control subjects. Differentially expressed gene analysis in four different T cell subsets from PNH and healthy control subjects showed distinct transcriptional profiles, depending on the T cell subsets. By pathway analysis, we identified novel signaling pathways in T cell subsets from PNH, including increased gene expression involved in TNFR, IGF1, NOTCH, AP-1, and ATF2 pathways. Dysregulation of several candidate genes (JUN, TNFAIP3, TOB1, GIMAP4, GIMAP6, TRMT112, NR4A2, CD69, and TNFSF8) was validated by quantitative real-time RT-PCR and flow cytometry. We have demonstrated molecular signatures associated with positive and negative regulators in T cells, suggesting novel pathophysiologic mechanisms in PNH. These pathways may be targets for new strategies to modulate T cell immune responses in BM failure." @default.
- W2668879080 created "2017-06-30" @default.
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- W2668879080 date "2017-07-15" @default.
- W2668879080 modified "2023-10-16" @default.
- W2668879080 title "T Cell Transcriptomes from Paroxysmal Nocturnal Hemoglobinuria Patients Reveal Novel Signaling Pathways" @default.
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- W2668879080 doi "https://doi.org/10.4049/jimmunol.1601299" @default.
- W2668879080 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5543699" @default.
- W2668879080 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28630090" @default.
- W2668879080 hasPublicationYear "2017" @default.
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