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Illuminating (Htlv-1)-Induced Adult T-Cell Leukemia/Lymphoma Transcriptomic Signature: A Systems Virology Approach Publisher Pubmed



Forghaniramandi MM1 ; Mostafavi B2, 6 ; Bahavar A3 ; Dehghankar M1 ; Siami Z4, 5 ; Mozhgani SH6, 7
Authors
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Authors Affiliations
  1. 1. Student Research Committee, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
  2. 2. Biomedical Engineering Department, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Tehran, Iran
  3. 3. Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
  4. 4. Department Infectious Disease and Tropical Medicine, Ziaeian Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Infectious Diseases, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
  6. 6. Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
  7. 7. Non-Communicable Disease Research Center, Alborz University of Medical Sciences, Karaj, Iran

Source: Virus Research Published:2023


Abstract

Background: Adult T-cell leukemia/lymphoma (ATLL) is a poor prognosis malignancy of peripheral T-cells caused by human T-cell leukemia virus type 1 (HTLV-1). The low survival rates observed in the patients are the result of the lack of sufficient knowledge about the disease pathogenesis. Methods: In the present study, we first identified differentially expressed genes in ATLL patients and the cellular signaling pathways affected by them. Then, genes of these pathways were subjected to more comprehensive evaluations, including WGCNA and module validation studies on five external datasets. Finally, potential biomarkers were selected for qRT-PCR validation. Results: Thirteen signaling pathways, including Apoptosis, Human T-cell leukemia virus 1 infection, IL-17 signaling pathway, pathways in cancer, T cell receptor signaling pathway, Th1 and Th2 cell differentiation, and seven others were selected for deeper investigations. Results of our in-depth bioinformatics evaluations, highlighted pathways related to regulation of immune responses, T-cell receptor and activation, regulation of cell signaling receptors and messengers, Wnt signaling pathway, and apoptosis as key players in ATLL pathogenesis. MAPK3, PIK3CD, KRAS, NFKB1, TNF, PLCB3, PLCB2, PLCB1, MAPK11, JUN, ITPR1, ADCY1, GNAQ, ADCY3, ADCY4, CHEK1, CCND1, SOS2, BAX, FOS and GNA12 were identified as possible biomarkers. Upregulation of ADCY1 and ADCY3 genes was confirmed via qRT-PCR. Conclusions: In this study, we performed a deep bioinformatic examination on a limited set of genes with high probabilities of involvement in the pathogenesis of ATLL. Our results highlighted signaling pathways and genes with potential key roles in disease formation and resistance against current treatment strategies. Further studies are required to test the possible benefits of highlighted genes as biomarkers and targets of treatment. © 2023