Tuba KABASAKAL, Mustafa Ertan AY, Kenan ÇEVİK, Anıl TOMBAK, Özlem İZCİ AY, Mehmet Emin ERDAL

CCAAT Enhancer-binding Protein Alpha (CEBPA) Gene Expression in a Cohort of Turkish Patients with Multiple Myeloma

OBJECTIVE Hematopoiesis is regulated and maintained by the function of the particular transcription factors. CCAAT enhancer-binding protein alpha (CEBPA), an important transcription factor, has a part in the regulation of cell cycle, granulocytic differentiation, and more. The possible role of CEBPA in multiple myeloma (MM) development has not been clarified so far. Therefore, this study aimed to explore the relationship between the expression levels of the CEBPA gene in Turkish patients diagnosed with MM. METHODS Using quantitative real-time PCR, the expression level of the CEBPA gene was examined in the bone marrow samples of 44 MM patients and 13 healthy controls. Statistical analyses were performed using SPSS, 13.3.1, and p

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1. Smith CJ, Ambs S, Landgren O. Biological determi nants of health disparities in multiple myeloma. Blood Cancer J 2018;8(9):1–7.
2. Weinhold N, Heuck CJ, Rosenthal A, Thanendrarajan S, Stein CK, Van Rhee F, et al. Clinical value of molecu lar subtyping multiple myeloma using gene expression profiling. Leukemia 2016;30(2):423–30.
3. Prideaux SM, O’Brien EC, Chevassut, TJ. The ge netic architecture of multiple myeloma. Adv Hematol 2014;2014:864058.
4. Soliman AM, Lin TS, Mahakkanukrauh P, Das S. Role of microRNAs in diagnosis, prognosis and management of multiple myeloma. Int J Mol Sci 2020;21(20):7539.
5. Manier S, Salem KZ, Park J, Landau DA, Getz G, Gho brial IM. Genomic complexity of multiple myeloma and its clinical implications. Nat Rev Clin Oncol 2017;14(2):100–13.
6. Barwick BG, Gupta VA, Vertino PM, Boise LH. Cell of origin and genetic alterations in the pathogenesis of multiple myeloma. Front Immunol 2019;10:1121.
7. Neuse CJ, Lomas OC, Schliemann C, Shen YJ, Manier S, Bustoros M, et al. Genome instability in multiple myeloma. Leukemia 2020;34(11):2887–97.
8. Pabst T, Mueller BU. Complexity of CEBPA dysregu lation in human acute myeloid leukemia. Clin Cancer Res 2009;15(17):5303–7.
9. Szmajda D, Krygier A, Jamroziak K, Żebrowska Nawrocka M, Balcerczak E. Expression level of CEBPA gene in acute lymphoblastic leukemia individuals. Sci Rep 2019;9(1):15640.
10.Barberi T, Cui C, Friedman, AD. C/EBPα induces Ebf1 gene expression in common lymphoid progenitors. PLoS One 2020;15(12):e0244161.
11.Johnson PF. Molecular stop signs: Regulation of cell cycle arrest by C/EBP transcription factors. J Cell Sci 2005;118(12):2545–55.
12.Gholami M, Bayat S, Manoochehrabadi S. Investi gation of CEBPA and CEBPA-AS genes expression in acute myeloid leukemia. Rep Biochem Mol Biol 2019;7(2):136.
13.Barbagallo D, Condorelli AG, Piro S. CEBPA exerts a specific and biologically important proapoptotic role in pancreatic β cells through its downstream network targets. Mol Biol Cell 2014;25(16):2333–41.
14.Koschmieder S, Halmos B, Levantini E, Tenen DG. Dysregulation of the C/EBPα differentiation pathway in human cancer. J Clin Oncol 2009;27(4):619–28.
15.Lourenço AR, Coffer PJ. A tumor suppressor role for C/EBPα in solid tumors: More than fat and blood. Oncogene 2017;36(37):5221–30.
16.Hasemann MS, Lauridsen FK, Waage J, Jakobsen JS, Frank AK, Schuster MB, et al. C/EBPα is required for long-term self-renewal and lineage priming of hematopoietic stem cells and for the maintenance of epigenetic configurations in multipotent progenitors. PLoS Genet 2014;10(1):e1004079.
17.Jones LC, Lin ML, Chen SS, Krug U, Hofmann WK, Lee S, et al. Expression of C/EBPβ from the C/ebp α gene locus is sufficient for normal hematopoiesis in vivo. Blood 2020;99(6):2032–6.
18.Chapiro E, Russell L, Radford-Weiss I, Bastard C, Lessard M, Struski S, et al. Overexpression of CEBPA resulting from the translocation t (14;19) (q32;q13) of human precursor B acute lymphoblastic leukemia. Blood 2006;108(10):3560–3.
19.Collombet S, van Oevelen C, Ortega JL, Abou-Jaoudé W, Di Stefano B, Thomas-Chollier M, et al. Logical modeling of lymphoid and myeloid cell specification and transdifferentiation. Proc Natl Acad Sci USA 2017;114(23):5792–9.
20.Fuchs O, Provaznikova D, Kocova M, , Kostecka A, Cvekova P, Neuwirtova R, et al. CEBPA polymor phisms and mutations in patients with acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and non-Hodgkin’s lymphoma. Blood Cells Mol Dis 2008;40(3):401–5.
21.Zang YZ, Chen XL, Bai YL, Zhang WH, Yu RH. Ex pression and clinical significance of C/EBPα gene in elderly multiple myeloma. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2019;27(1):123–8.
22.Han X, Zhou DB, Duan MH, Hua BL, Wang X, Zhang JP, et al. C/EBPα in multiple myeloma patients may lead to increased hepcidin. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2014;22(5):1316–20.