Advances in Cancer Immunotherapy and Stem Cell Research

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DOI :10.26650/B/LS17LS30.2025.038.008   IUP :10.26650/B/LS17LS30.2025.038.008    Tam Metin (PDF)

Biological Function of Activation-induced Cytidine Deaminase (Aid): Potential Role in B-Cell Malignancies

Metin Yusuf Gelmez, Melih Aktan, Günnur Deniz

Activation-induced cytidine deaminase (AID) enzyme is discovered by Japanese scientist Tasuku Honjo and his team. AID, a member of the cytidine deaminase family, converts cytosine to uracil in DNA. AID play a role in the process of generating antibodies with higher affinity for antigens in B lymphocytes is called “affinity maturation”, and the conversion of antibodies from the IgM isotype to the IgG, IgA, or IgE isotypes is called “isotype switching”. Recent studies have shown that the AID can cause mutations and DNA breaks not only in the IgVH and Ig C regions but also in non-immunoglobulin genes. AID is known the first mutator enzyme and recent studies have indicated that AID is responsible for genomic instability like point mutation, translocation in hematologic malignancies and may affect the clinical course of the disease. AID ”knock-out” mice studies showed that AID plays a role in the development of Burkitt lymphoma by creating dsDNA breaks and causing translocations in the IgH/c-myc. It was shown that there is a correlation between AID expression and poor prognosis in various B-cell lymphomas and leukemias. Additionally, chronic lymphocytic leukemia (CLL) patients who do not have somatic hypermutation in the IgVH genes have a worse clinical course. In CLL patients with chromosomal deletion, the expression of the AID gene is higher than in patients without these deletions, and that the AID gene may be responsible for these deletions. According to common findings, AID is necessary for tumorigenesis and affects the prognosis in patients with B-cell lymphoma and leukemia. 


Anahtar Kelimeler: Activation-induced cytidine deaminase, AID, B-cell malignancies

Referanslar

  • 1. Muramatsu M, Sankaranand VS, Anant S, Sugai M, Kinoshita K, Davidson NO, Honjo T. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells. J Biol Chem. 1999;274(26):18470-476. google scholar
  • 2. Zan H, Casali P. Regulation of Aicda expression and AID activity. Autoimmunity. 2013;46(2):83-101. google scholar
  • 3. Revy P, Muto T, Levy Y, Geissmann F, Plebani A, Sanal O, et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell. 2000;102(5):565-75. google scholar
  • 4 . Gutierrez-Melo N, Baumjohann D . T follicular helper cells in cancer. Trends Cancer. 2023;9(4):309-25. google scholar
  • 5. Stebegg M, Kumar SD, Silva-Cayetano A, Fonseca VR, Linterman MA, Graca L. Regulation of the germinal center response. Front Immunol. 2018;25(9):2469. google scholar
  • 6. Brar SS, Sacho EJ, Tessmer I, Croteau DL, Erie DA, Diaz M. Activation-induced deaminase, AID, is catalytically active as a monomer on single-stranded DNA. DNA Repair. 2008;7(1):77-87. google scholar
  • 7. De Souza Rios LA, Cloete B, Mowla S. Activation-induced cytidine deaminase: in sickness and in health. J Cancer Res Clin Oncol. 2020;146(11):2721-730. google scholar
  • 8. Teater M, Dominguez PM, Redmond D, Chen Z, Ennishi D, Scott DW, et al. AICDA drives epigenetic heterogeneity and accelerates germinal center-derived lymphomagenesis. Nat Commun. 2018;9(1):222. google scholar
  • 9. Kuraoka M, Meffre E, Kelsoe G. The first B-Cell tolerance checkpoint in mice and humans: control by AID. Adv Immunol. 2018;139:51-92. google scholar
  • 10. Longerich S, Basu U, Alt F, Storb U. AID in somatic hypermutation and class switch recombination. Curr Opin Immunol. 2006;18(2):164-74. google scholar
  • 11. Gazumyan A, Timachova K, Yuen G, Siden E, Di Virgilio M, Woo EM, et al. Amino-terminal phosphorylation of activation-ınduced cytidine deaminase suppresses c-myc/IgH translocation. Mol Cell Biol. 2011;31(3):442-9. google scholar
  • 12. Aoufouchi, S, Faili A, Zober C, D’Orlando O, Weller S, Weill JC, et al., Proteasomal degradation restricts the nuclear lifespan of AID. J Exp Med, 2008;205(6):1357-68. google scholar
  • 13. Choudhary M, Tamrakar A, Singh AK, Jain M, Jaiswal A, Kodgire P. AID Biology: A pathological and clinical perspective. Int Rev Immunol. 2018;37(1):37-56. google scholar
  • 14. Mu Y, Zelazowska MA, McBride KM. Phosphorylation promotes activation-induced cytidine deaminase activity at the Myc oncogene. J Exp Med. 2017;214(12):3543-52. google scholar
  • 15. Orthwein A. Di Noia JM. Activation induced deaminase: how much and where? Semin Immunol, 2012;24(4):246-54. google scholar
  • 16. Park S, Kim P, Lee K, Lee SH, Seo GY, Yoo YC, et al. APRIL stimulates NF-B-mediated HoxC4 induction for AID expression in mouse B cells. Cytokine 2013;61(2):608-13. google scholar
  • 17. Wu X, Darce J, Chang SK, Nowakowski GS, Jelineket DF. Alternative splicing regulates activation-induced cytidine deaminase (AID): implications for suppression of AID mutagenic activity in normal and malignant B cells. Blood, 2008;112(12):4675-82. google scholar
  • 18. Kaufman M, Yan XJ, Li W, Ghia EM, Langerak AW, Rassenti LZ, et al. Impact of the types and relative quantities of İGHV gene mutations in predicting prognosis of patients with chronic lymphocytic leukemia. Front Oncol. 2022; 12(12):897280. google scholar
  • 19. Çakan E, Gunaydin G. Activation induced cytidine deaminase: an old friend with new faces. Front İmmunol. 2022;27(13):965312. google scholar
  • 20. Yu K. AİD function in somatic hypermutation and class switch recombination. Acta Biochim Biophys Sin. 2022;54(6):759-66. google scholar
  • 21. Alaggio R, Amador Ç, Anagnostopoulos İ, Attygalle AD, Araujo İBO, et al. The 5th edition of the world health organization classification of hematolymphoid tumors: Lymphoid Neoplasms. Leukemia. 2022;36(7):1720-48. google scholar
  • 22. Segal GH, Kjeldsberg ÇR. Practical lymphoma diagnosis: an approach to using the information organized in the REAL proposal. Revised European-American lymphoid neoplasm. Anat Pathol. 1998;3:147-68. google scholar
  • 23. Tosi P, Barosi G, Lazzaro Ç, et al. Çonsensus conference on the management of tumour lysis syndrome. Haematologica. 2008;93(12):1877-85. google scholar
  • 24. Kotani A, Kakazu N, Tsuruyama T, Okazaki İ, Muramatsu M, Kinoshita K, Nagaoka H, et al., Activation-induced cytidine deaminase (AİD) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice. Proc Natl Acad Sci USA. 2007;104(5):1616-10. google scholar
  • 25. Oppezzo P, Navarrete M, Çhiorazzi N. AİD in chronic lymphocytic leukemia: İnduction and action during disease progression. Front Oncol. 2021;11:634383. google scholar
  • 26. Gelmez MY, Teker AB, Aday AD, Yavuz AS, Soysal T, Deniz G, Aktan M. Analysis of activation-induced cytidine deaminase mRNA levels in patients with chronic lymphocytic leukemia with different cytogenetic status. Leuk Lymphoma. 2014;55(2):326-30. google scholar
  • 27. Gelmez MY, Çoskunpinar E, Saracoglu B, Deniz G, Aktan M. İnvestigation of AİD, dicer, and drosha expressions in patients with chronic lymphocytic leukemia. İmmunol İnvest. 2017;46(5):433-46. google scholar


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