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. 2023 Nov 1;27(6):357-65.
doi: 10.61186/ibj.3754. Epub 2022 Jul 31.

Increased Expression of NOTCH-1 and T Helper Cell Transcription Factors in Patients with Acquired Aplastic Anemia

Vandana Sharma  1 , Manju Namdeo  2 , Prabin Kumar  2 , Dipendra Kumar Mitra  2 , Parthaprasad Chattopadhyay  3 , Sudha Sazawal  1 , Rekha Chaubey  1 , Renu Saxena  1 , Uma Kanga  2 , Tulika Seth  1
Affiliations

Increased Expression of NOTCH-1 and T Helper Cell Transcription Factors in Patients with Acquired Aplastic Anemia

Vandana Sharma et al. Iran Biomed J. .

Abstract

Background: Acquired aplastic anemia 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 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 PB 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 SAA and VSAA than NSAA 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.

Keywords: Anemia; Aplastic; Transcription factors.

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Conflict of interest statement

None declared.

Figures

Fig. 1
Fig. 1
Box and whisker plots representing the relative mRNA expression of (A) NOTCH-1, (B) DLL-1, (C) JAG-1, (D) T-BET, (E) GATA-3, and (F) ROR-γT in PB and BM of aAA patients vs. healthy controls. N, the number of patients/controls
Fig. 2
Fig. 2
Box and whisker plots representing the relative mRNA expression of (A) NOTCH-1, (B) T-BET, (C) GATA-3, and (D) ROR-γT in PB and BM of NSAA vs. SAA + VSAA patients. N, the number of patients; R, correlation co-efficient; P, p value
Fig. 3
Fig. 3
Correlation analysis between relative mRNA expression of NOTCH-1 and (A) T-BET, (B) GATA-3, and (C) ROR-γT in aAA patients. R, correlation co-efficient; N, number of patients
Fig. 4
Fig. 4
Correlation analysis between the relative mRNA expression of NOTCH-1, T-BET, GATA-3, and ROR-γT with hematological parameters of patients. N, number of patients; R, correlation co-efficient; P, p value
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