Aberrant Activation-Induced Cytidine Deaminase
Gene Expression Links BCR/ABL1-Negative Classical
Myeloproliferative Neoplasms

gelmez, metin yusuf; Daglar Aday, Aynur; YAVUZ, AKIF SELIM; Nalcaci, Meliha; hancer, veysel sabri; Dermenci, Hasan; Akadam Teker, Ayşegül Başak

doi:10.4274/haseki.galenos.2022.8133

Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms

Hasan DERMENCİ, (Türkiye Sağlık Bilimleri Üniversitesi, Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Hematoloji Kliniği, İstanbul, Türkiye)

Aynur DAĞLAR ADAY, (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Tıbbi Genetik Anabilim Dalı, İstanbul, Türkiye)

Ayşegül Başak AKADAM TEKER, (Giresun Üniversitesi Tıp Fakültesi Tıbbi Genetik Anabilim Dalı, Giresun, Türkiye)

Veysel HANÇER, (İstinye Üniversitesi Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, İstanbul, Türkiye)

Metin Yusuf GELMEZ, (İstanbul Üniversitesi, Deneysel Tıp Enstitüsü, İmmünoloji Anabilim Dalı, İstanbul, Türkiye)

Meliha NALÇACI, (İstanbul Üniversitesi, Deneysel Tıp Enstitüsü, İmmünoloji Anabilim Dalı, İstanbul, Türkiye)

Akif Selim YAVUZ (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Hematoloji Anabilim Dalı, İstanbul, Türkiye)

Haseki Tıp Bülteni

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Yıl: 2022 Cilt: 60 Sayı: 3 Sayfa Aralığı: 228 - 233 Metin Dili: İngilizce DOI: 10.4274/haseki.galenos.2022.8133 İndeks Tarihi: 05-07-2022

Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms

Öz:

Aim: Activation-induced cytidine deaminase (AID) has been associated with tumor initiation and development because of its ability to generate DNA damage and somatic mutations that cause genomic instability. This study aimed to investigate the relationship between AID expression levels and the risk of developing BCR/ABL1-negative myeloproliferative neoplasms (MPNs) by comparing the AID expression levels of the patients and controls. Methods: This case-control study was conducted on 117 cases (64 essential thrombocythemia, 23 primary myelofibrosis, and 30 polycythemia vera) with MPNs and 69 healthy controls. The JAK2 V617F somatic mutation analysis was performed using a real-time polymerase chain reaction (RT-PCR). The relative expression levels of AID in the patient and the control groups were analyzed using quantitative RT-PCR and the 2-ΔΔCT method. Results: AID expression levels were significantly higher in the patient group compared to the control group (p<0.001). AID expression levels were higher in patients with the JAK2 V617F mutation compared to patients without the mutation, but the difference was not statistically significant. Conclusion: The results of our study suggest that although overexpression of AID does not seem to support the JAK2 driver gene, it may contribute to the development of MPNs through other mechanisms.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Tefferi A. Myeloproliferative neoplasms: A decade of discoveries and treatment advances. Am J Hematol 2016;91:50-8.
2. Grinfeld J, Nangalia J, Green AR. Molecular determinants of pathogenesis and clinical phenotype in myeloproliferative neoplasms. Haematologica 2017;102:7-17.
3. Nangalia J, Green AR. Myeloproliferative neoplasms: from origins to outcomes. Blood 2017;130:2475-83.
4. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005;365:1054-61.
5. Steensma DP, Dewald GW, Lasho TL, et al. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both “atypical” myeloproliferative disorders and myelodysplastic syndromes. Blood 2005;106:1207-9.
6. Abdel-Wahab O, Manshouri T, Patel J, et al. Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. Cancer Res 2010;70:447-52.
7. Teng B, Burant CF, Davidson NO. Molecular cloning of an apolipoprotein B messenger RNA editing protein. Science 1993;260:1816-9.
8. Muñoz DP, Lee EL, Takayama S, et al. Activation-induced cytidine deaminase (AID) is necessary for the epithelialmesenchymal transition in mammary epithelial cells. Proc Natl Acad Sci U S A 2013;110:E2977-86.
9. Sablitzky F, Wildner G, Rajewsky K. Somatic mutation and clonal expansion of B cells in an antigen-driven immune response. EMBO J 1985;4:345-50.
10. Hu D, Zheng H, Liu H, et al. Immunoglobulin expression and its biological significance in cancer cells. Cell Mol Immunol 2008;5:319-24.
11. Chen Z, Qiu X, Gu J. Immunoglobulin expression in non-lymphoid lineage and neoplastic cells. Am J Pathol 2009;174:1139-48.
12. Rios LAS, Cloete B, Mowla S. Activation-induced cytidine deaminase: in sickness and in health. J Cancer Res Clin Oncol 2020;146:2721-30.
13. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 2008;22:14-22.
14. Rebhandl S, Huemer M, Greil R, Geisberger R. AID/APOBEC deaminases and cancer. Oncoscience 2015;2:320-33.
15. Pavri R, Nussenzweig MC. AID targeting in antibody diversity. Adv Immunol 2011;110:1-26.
16. Hancer VS, Kose M, Diz-Kucukkaya R, Yavuz AS, Aktan M. Activation-induced cytidine deaminase mRNA levels in chronic lymphocytic leukemia. Leuk Lymphoma 2011;52:79- 84.
17. Edry E, Azulay-Debby H, Melamed D. TOLL-like receptor ligands stimulate aberrant class switch recombination in early B cell precursors. Int Immunol 2008;20:1575-85.
18. Feldhahn N, Henke N, Melchior K, et al. Activation-induced cytidine deaminase acts as a mutator in BCR-ABL1- transformed acute lymphoblastic leukemia cells. J Exp Med 2007;204:1157-66.
19. Nakamura M, Sugita K, Sawada Y, Yoshiki R, Hino R, Tokura Y. High levels of activation-induced cytidine deaminase expression in adult T-cell leukaemia/lymphoma. Br J Dermatol 2011;165:437-9.
20. Shinmura K, Igarashi H, Goto M, et al. Aberrant expression and mutation-inducing activity of AID in human lung cancer. Ann Surg Oncol 2011;18:2084-92.
21. Klemm L, Duy C, Iacobucci I, et al. The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia. Cancer Cell 2009;16:232-45.
22. Maura F, Rustad EH, Yellapantula V, et al. Role of AID in the temporal pattern of acquisition of driver mutations in multiple myeloma. Leukemia 2020;34:1476-80.
23. Morande PE, Yan XJ, Sepulveda J, et al. AID overexpression leads to aggressive murine CLL and nonimmunoglobulin mutations that mirror human neoplasms. Blood 2021;138:246-58.
24. Che Z, Fan J, Zhou Z, et al. Activation-Induced Cytidine Deaminase Expression Facilitates the Malignant Phenotype and Epithelial-to-Mesenchymal Transition in Clear Cell Renal Cell Carcinoma. DNA Cell Biol 2020;39:1299-312.
25. Torun ES, Dağlar Aday A, Nalçaci M. Activationinduced cytidine deaminase expression in patients with myelodysplastic syndrome and its relationship with prognosis and treatment. Turk J Med Sci 2021;51:2451-60.
26. Marusawa H. Aberrant AID expression and human cancer development. Int J Biochem Cell Biol 2008;40:1399-402.
27. Robbiani DF, Bunting S, Feldhahn N, et al. AID produces DNA double-strand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations. Mol Cell 2009;36:631-41.
28. Kunimoto H, McKenney AS, Meydan C, et al. Aid is a key regulator of myeloid/erythroid differentiation and DNA methylation in hematopoietic stem/progenitor cells. Blood 2017;129:1779-90.
29. Li H, Li Q, Ma Z, et al. AID modulates carcinogenesis network via DNA demethylation in bladder urothelial cell carcinoma. Cell Death Dis 2019;10:251.
30. Vile RG, Melcher A, Pandha H, Harrington KJ, Pulido JS. APOBEC and Cancer Viroimmunotherapy: Thinking the Unthinkable. Clin Cancer Res 2021;27:3280-90.
31. Sakano K, Oikawa S, Hasegawa K, Kawanishi S. Hydroxyurea induces site-specific DNA damage via formation of hydrogen peroxide and nitric oxide. Jpn J Cancer Res 2001;92:1166-74.

APA	Dermenci H, Daglar Aday A, Akadam Teker A, hancer v, gelmez m, Nalcaci M, YAVUZ A (2022). Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms. , 228 - 233. 10.4274/haseki.galenos.2022.8133
Chicago	Dermenci Hasan,Daglar Aday Aynur,Akadam Teker Ayşegül Başak,hancer veysel sabri,gelmez metin yusuf,Nalcaci Meliha,YAVUZ AKIF SELIM Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms. (2022): 228 - 233. 10.4274/haseki.galenos.2022.8133
MLA	Dermenci Hasan,Daglar Aday Aynur,Akadam Teker Ayşegül Başak,hancer veysel sabri,gelmez metin yusuf,Nalcaci Meliha,YAVUZ AKIF SELIM Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms. , 2022, ss.228 - 233. 10.4274/haseki.galenos.2022.8133
AMA	Dermenci H,Daglar Aday A,Akadam Teker A,hancer v,gelmez m,Nalcaci M,YAVUZ A Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms. . 2022; 228 - 233. 10.4274/haseki.galenos.2022.8133
Vancouver	Dermenci H,Daglar Aday A,Akadam Teker A,hancer v,gelmez m,Nalcaci M,YAVUZ A Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms. . 2022; 228 - 233. 10.4274/haseki.galenos.2022.8133
IEEE	Dermenci H,Daglar Aday A,Akadam Teker A,hancer v,gelmez m,Nalcaci M,YAVUZ A "Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms." , ss.228 - 233, 2022. 10.4274/haseki.galenos.2022.8133
ISNAD	Dermenci, Hasan vd. "Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms". (2022), 228-233. https://doi.org/10.4274/haseki.galenos.2022.8133

APA	Dermenci H, Daglar Aday A, Akadam Teker A, hancer v, gelmez m, Nalcaci M, YAVUZ A (2022). Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms. Haseki Tıp Bülteni, 60(3), 228 - 233. 10.4274/haseki.galenos.2022.8133
Chicago	Dermenci Hasan,Daglar Aday Aynur,Akadam Teker Ayşegül Başak,hancer veysel sabri,gelmez metin yusuf,Nalcaci Meliha,YAVUZ AKIF SELIM Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms. Haseki Tıp Bülteni 60, no.3 (2022): 228 - 233. 10.4274/haseki.galenos.2022.8133
MLA	Dermenci Hasan,Daglar Aday Aynur,Akadam Teker Ayşegül Başak,hancer veysel sabri,gelmez metin yusuf,Nalcaci Meliha,YAVUZ AKIF SELIM Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms. Haseki Tıp Bülteni, vol.60, no.3, 2022, ss.228 - 233. 10.4274/haseki.galenos.2022.8133
AMA	Dermenci H,Daglar Aday A,Akadam Teker A,hancer v,gelmez m,Nalcaci M,YAVUZ A Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms. Haseki Tıp Bülteni. 2022; 60(3): 228 - 233. 10.4274/haseki.galenos.2022.8133
Vancouver	Dermenci H,Daglar Aday A,Akadam Teker A,hancer v,gelmez m,Nalcaci M,YAVUZ A Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms. Haseki Tıp Bülteni. 2022; 60(3): 228 - 233. 10.4274/haseki.galenos.2022.8133
IEEE	Dermenci H,Daglar Aday A,Akadam Teker A,hancer v,gelmez m,Nalcaci M,YAVUZ A "Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms." Haseki Tıp Bülteni, 60, ss.228 - 233, 2022. 10.4274/haseki.galenos.2022.8133
ISNAD	Dermenci, Hasan vd. "Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms". Haseki Tıp Bülteni 60/3 (2022), 228-233. https://doi.org/10.4274/haseki.galenos.2022.8133