Iranian Biomedical Journal

en Increased Expression of NOTCH-1 and T Helper Cell Transcription Factors in Patients with Acquired Aplastic Anemia Cancer Biology Cancer Biology مقاله کامل Full Length/Original Article 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. Anemia, Aplastic, Transcription factors 357 365 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-4973-1&slc_lang=en&sid=1 Vandana Sharma vsharma1087@gmail.com 0000-0001-8054-8452 No Department of Hematology, All India Institute of Medical Sciences, New Delhi, India Manju Namdeo manjunamdeo@gmail.com 0000-0002-2857-1310 No Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India Prabin Kumar raiprabin79@gmail.com 0000-0003-4977-0076 No Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India Dipendra Kumar Mitra salilmitra2@gmail.com 0000-0003-0572-7885 No Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India Parthaprasad Chattopadhyay parthoaiims@hotmail.com 0000-0002-0108-2920 No Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India Sudha Sazawal sudhasazawal59@gmail.com 0000-0002-6313-241X No Department of Hematology, All India Institute of Medical Sciences, New Delhi, India Rekha Chaubey drrekhacgupta@gmail.com 0000-0003-1937-1971 No Department of Hematology, All India Institute of Medical Sciences, New Delhi, India Renu Saxena renusaxena@outlook.com 0000-0003-1532-297X No Department of Hematology, All India Institute of Medical Sciences, New Delhi, India Uma Kanga umakanga@hotmail.com 0000-0001-9437-0835 No Department of Hematology, All India Institute of Medical Sciences, New Delhi, India Tulika Seth drtulikaseth@gmail.com 0000-0001-9760-7957 Yes Department of Hematology, All India Institute of Medical Sciences, New Delhi, India