LinkedIn

 آمار

تعداد نشریات20
تعداد شماره‌ها1,149
تعداد مقالات10,518
تعداد مشاهده مقاله45,416,090
تعداد دریافت فایل اصل مقاله11,291,759
Mohammadi, Maryam, Asgarian-Omran, Hossein, Najafi, Behnam, Najafi, Ahmad, Valadan, Reza, Karami, Hossein, Naderisoraki, Mohammad, Alizadeforutan, Maryam, Shekarriz, Ramin, Tehrani, Mohsen. (1402). Evaluation of mRNA Expressions of TOX and NR4As in CD8+ T cells in Acute Leukemia. سامانه مدیریت نشریات علمی, 20(4), 438-445. doi: 10.22034/iji.2023.97902.2537
Maryam Mohammadi; Hossein Asgarian-Omran; Behnam Najafi; Ahmad Najafi; Reza Valadan; Hossein Karami; Mohammad Naderisoraki; Maryam Alizadeforutan; Ramin Shekarriz; Mohsen Tehrani. "Evaluation of mRNA Expressions of TOX and NR4As in CD8+ T cells in Acute Leukemia". سامانه مدیریت نشریات علمی, 20, 4, 1402, 438-445. doi: 10.22034/iji.2023.97902.2537
Mohammadi, Maryam, Asgarian-Omran, Hossein, Najafi, Behnam, Najafi, Ahmad, Valadan, Reza, Karami, Hossein, Naderisoraki, Mohammad, Alizadeforutan, Maryam, Shekarriz, Ramin, Tehrani, Mohsen. (1402). 'Evaluation of mRNA Expressions of TOX and NR4As in CD8+ T cells in Acute Leukemia', سامانه مدیریت نشریات علمی, 20(4), pp. 438-445. doi: 10.22034/iji.2023.97902.2537
Mohammadi, Maryam, Asgarian-Omran, Hossein, Najafi, Behnam, Najafi, Ahmad, Valadan, Reza, Karami, Hossein, Naderisoraki, Mohammad, Alizadeforutan, Maryam, Shekarriz, Ramin, Tehrani, Mohsen. Evaluation of mRNA Expressions of TOX and NR4As in CD8+ T cells in Acute Leukemia. سامانه مدیریت نشریات علمی, 1402; 20(4): 438-445. doi: 10.22034/iji.2023.97902.2537

Evaluation of mRNA Expressions of TOX and NR4As in CD8+ T cells in Acute Leukemia

Iranian Journal of Immunology
مقاله 5، دوره 20، شماره 4، اسفند 2023، صفحه 438-445    اصل مقاله (674.54 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22034/iji.2023.97902.2537
نویسندگان
Maryam Mohammadi1؛ Hossein Asgarian-Omran1، 2؛ Behnam Najafi1؛ Ahmad Najafi1؛ Reza Valadan3؛ Hossein Karami4؛ Mohammad Naderisoraki4؛ Maryam Alizadeforutan2، 5؛ Ramin Shekarriz2، 5؛ Mohsen Tehrani* 1، 2
1Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
2Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
3Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
4Thalassemia Research Center (TRC), Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran.
5Department of Hematology and Oncology, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran.
چکیده
Background: Thymocyte selection-associated high mobility group box protein (TOX) and members of the nuclear receptor 4A (NR4A) are known as transcription factors involved in T cell exhaustion.
Objective: To evaluate the mRNA expression of TOX and NR4A1-3 in CD8+ T cells in acute leukemia.
Methods: Blood samples were obtained from 21 ALL and 6 AML patients as well as 20 control subjects. CD8+ T cells were isolated using MACS. Relative gene expression of TOX and NR4A1-3 was then evaluated using qRT-PCR.
Results: Comparison of mRNA expression of TOX in CD8+ T cells showed no significant difference among the study groups (p>0.05), while the expression of NR4A1 was significantly lower in AML patients than in the control group (p=0.0006). Also, the expression of NR4A2 and NR4A3 was significantly lower in both ALL (p=0.0049 and p=0.0005, respectively) and AML (p=0.0019 and p=0.0055, respectively) patients.
Conclusion: NR4As expressions were found to be lower in CD8+ T cells from patients with AML and ALL compared to controls, whereas the mRNA expression of TOX showed no significant difference. Although TOX and NR4As are associated with CD8+ T cell exhaustion in solid tumors, they might play different roles in acute leukemia, which requires further investigation.
کلیدواژه‌ها
Leukemia؛ NR4A؛ T cell Exhaustion؛ TOX
مراجع
  1. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15(8):486-99.
  2. Pearen MA, Ryall JG, Maxwell MA, Ohkura N, Lynch GS, Muscat GEO. The Orphan Nuclear Receptor, NOR-1, Is a Target of β-Adrenergic Signaling in Skeletal Muscle. Endocrinology. 2006;147(11):5217-27.
  3. Seo H, Chen J, González-Avalos E, Samaniego-Castruita D, Das A, Wang YH, et al. TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8(+) T cell exhaustion. Proc Natl Acad Sci U S A. 2019;116(25):12410-5.
  4. Chen J, López-Moyado IF, Seo H, Lio CJ, Hempleman LJ, Sekiya T, et al. NR4A transcription factors limit CAR T cell function in solid tumours. Nature. 2019;567(7749):530-4.
  5. Khan O, Giles JR, McDonald S, Manne S, Ngiow SF, Patel KP, et al. TOX transcriptionally and epigenetically programs CD8(+) T cell exhaustion. Nature. 2019;571(7764):211-8.
  6. Tessema M, Yingling CM, Grimes MJ, Thomas CL, Liu Y, Leng S, et al. Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers. PLoS One. 2012;7(4):e34850.
  7. Jabbour E, O'Brien S, Konopleva M, Kantarjian H. New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia. Cancer. 2015;121(15):2517-28.
  8. García-Escobar I, Sepúlveda J, Castellano D, Cortés-Funes H. Therapeutic management of chronic lymphocytic leukaemia: state of the art and future perspectives. Crit Rev Oncol Hematol. 2011;80(1):100-13.
  9. Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation. Immunity. 2016;44(5):989-1004.
  10. Doering TA, Crawford A, Angelosanto JM, Paley MA, Ziegler CG, Wherry EJ. Network analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memory. Immunity. 2012;37(6):1130-44.
  11. Kallies A, Zehn D, Utzschneider DT. Precursor exhausted T cells: key to successful immunotherapy? Nature Reviews Immunology. 2020;20(2):128-36.
  12. Philip M, Fairchild L, Sun L, Horste EL, Camara S, Shakiba M, et al. Chromatin states define tumour-specific T cell dysfunction and reprogramming. Nature. 2017;545(7655):452-6.
  13. Pauken KE, Sammons MA, Odorizzi PM, Manne S, Godec J, Khan O, et al. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science. 2016;354(6316):1160-5.
  14. Crabtree GR, Olson EN. NFAT signaling: choreographing the social lives of cells. Cell. 2002;109 Suppl:S67-79.
  15. Huang S, Liang C, Zhao Y, Deng T, Tan J, Zha X, et al. Increased TOX expression concurrent with PD-1, Tim-3, and CD244 expression in T cells from patients with acute myeloid leukemia. Cytometry B Clin Cytom. 2022;102(2):143-52.
  16. Lobbardi R, Pinder J, Martinez-Pastor B, Theodorou M, Blackburn JS, Abraham BJ, et al. TOX Regulates Growth, DNA Repair, and Genomic Instability in T-cell Acute Lymphoblastic Leukemia. Cancer Discov. 2017;7(11):1336-53.
  17. Boudreaux SP, Ramirez-Herrick AM, Duren RP, Conneely OM. Genome-wide profiling reveals transcriptional repression of MYC as a core component of NR4A tumor suppression in acute myeloid leukemia. Oncogenesis. 2012;1(7):e19.
  18. Wenzl K, Troppan K, Neumeister P, Deutsch AJ. The nuclear orphan receptor NR4A1 and NR4A3 as tumor suppressors in hematologic neoplasms. Curr Drug Targets. 2015;16(1):38-46.
  19. 19. Ando M, Ito M, Srirat T, Kondo T, Yoshimura A. Memory T cell, exhaustion, and tumor immunity. Immunol Med. 2020;43(1):1-9.
آمار
تعداد مشاهده مقاله: 779
تعداد دریافت فایل اصل مقاله: 574


سامانه مدیریت نشریات علمی. قدرت گرفته از سیناوب