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Biomedical Journal
Volume 27, Issue 6 (11-2023)
IBJ 2023, 27(6): 357-365 |
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Sharma V, Namdeo M, Kumar P, Kumar Mitra D, Chattopadhyay P, Sazawal S, et al . Increased Expression of NOTCH-1 and T Helper Cell Transcription Factors in Patients with Acquired Aplastic Anemia. IBJ 2023; 27 (6) :357-365
URL: http://ibj.pasteur.ac.ir/article-1-3754-en.html
URL: http://ibj.pasteur.ac.ir/article-1-3754-en.html
Vandana Sharma 
, Manju Namdeo , Prabin Kumar , Dipendra Kumar Mitra , Parthaprasad Chattopadhyay , Sudha Sazawal , Rekha Chaubey , Renu Saxena , Uma Kanga , Tulika Seth *
, Manju Namdeo , Prabin Kumar , Dipendra Kumar Mitra , Parthaprasad Chattopadhyay , Sudha Sazawal , Rekha Chaubey , Renu Saxena , Uma Kanga , Tulika Seth *
Abstract:
Background: Acquired aplastic anemia (aAA) is an autoimmune disease in which auto-aggressive T cells destroy hematopoietic progenitors. T-cell differentiation is controlled by transcription factors that interact with NOTCH-1, which influences the respective T-cell lineages. Notch signaling also regulates the bone marrow (BM) microenvironment. The present study aimed to assess the gene expressions of NOTCH-1 and T helper cell transcription factors in the acquired aplastic anemia patients.
Methods: Using quantitative real-time PCR, we studied the mRNA expression level for NOTCH-1, its ligands (DLL-1 and JAG-1), and T helper cell transcription factors (T-BET, GATA-3, and ROR-γt) in both peripheral blood and BM of aAA patients and healthy controls. Further, patients of aplastic anemia were stratified by their disease severity as per the standard criteria.
Results: The mRNA expression level of NOTCH-1, T-BET, GATA-3, and ROR-γT genes increased in aAA patients compared to healthy controls. There was no significant difference in the mRNA expression of Notch ligands between patients and controls. The mRNA expression level of the above-mentioned genes was found to be higher in severe aplastic anemia and very severe aplastic anemia than non-severe aplastic anemia patients. In addition, NOTCH-1 and T helper cell-specific transcription factors enhanced in aAA. We also observed a significant correlation between the genes and hematological parameters in patients.
Conclusion: The interaction between NOTCH-1, T-BET, GATA-3, and
ROR-γT might lead to the activation, proliferation, and polarization of T helper cells and subsequent BM destruction. The mRNA expression levels of genes varied with disease severity, which may contribute to pathogenesis of aAA.
Methods: Using quantitative real-time PCR, we studied the mRNA expression level for NOTCH-1, its ligands (DLL-1 and JAG-1), and T helper cell transcription factors (T-BET, GATA-3, and ROR-γt) in both peripheral blood and BM of aAA patients and healthy controls. Further, patients of aplastic anemia were stratified by their disease severity as per the standard criteria.
Results: The mRNA expression level of NOTCH-1, T-BET, GATA-3, and ROR-γT genes increased in aAA patients compared to healthy controls. There was no significant difference in the mRNA expression of Notch ligands between patients and controls. The mRNA expression level of the above-mentioned genes was found to be higher in severe aplastic anemia and very severe aplastic anemia than non-severe aplastic anemia patients. In addition, NOTCH-1 and T helper cell-specific transcription factors enhanced in aAA. We also observed a significant correlation between the genes and hematological parameters in patients.
Conclusion: The interaction between NOTCH-1, T-BET, GATA-3, and
ROR-γT might lead to the activation, proliferation, and polarization of T helper cells and subsequent BM destruction. The mRNA expression levels of genes varied with disease severity, which may contribute to pathogenesis of aAA.
Type of Study: Full Length/Original Article |
Subject:
Cancer Biology
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