Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 5, August, p. 761–765

doi: 10.17219/acem/63087

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

The role of certain gene polymorphisms involved in the apoptotic pathways in polycythemia vera and essential thrombocytosis

Gurbet Dogru1,A,B,C,D, Ozlem Izci Ay1,A,C,D, Mehmet Emin Erdal1,C,E, Mustafa Ertan Ay1,C,D,E, Anıl Tombak2,B,C, Umit Karakas1,E,F

1 Department of Medical Biology and Genetics, Faculty of Medicine, Mersin University, Mersin, Turkey

2 Department of Heamatology, Faculty of Medicine, Mersin University, Mersin, Turkey


Background. Polycythemia vera (PV) and essential thrombocytosis (ET) are hematological disorders characterized by excessive production of mature and functional blood cells. These cellular disorders are thought to be associated with impaired apoptosis, which is one of the major cellular death mechanisms in hematopoietic cells.
Objectives. In this study, our objective was to examine the association between potential polymorphisms of the Bcl 2, Bax, Fas and Fas Ligand genes involved in apoptosis and the occurrence of PV and ET.
Material and Methods. A total of 93 patients diagnosed with PV (n = 38) or ET (n = 55) at the Department of Hematology were included in this study, and 93 healthy individuals served as controls. DNA isolation was performed in blood samples obtained from both groups of subjects to determine the Bcl 2, Bax, Fas, and Fas L genotypes using the real-time PCR method.
Results. No statistically significant differences between controls and patients were found in terms of Fas -670 G > A (rs1800682), Fas -1377 G > A (rs2234767), Fas L IVS2 -124 A > G (rs5030772), Bax -248 G > A (rs4645878) and Bcl 2 -938 C > A (rs2279115) polymorphisms, genotypes, and allele frequency (p > 0.05).
Conclusion. The results show that polymorphisms in the Bcl 2, Bax, Fas, and Fas Ligand genes involved in the apoptotic pathways may not play a role in the pathogenesis of PV and ET.

Key words

polymorphism, polycythemia vera (PV), essential thrombocytosis (ET), apoptotic pathway genes

References (21)

  1. Kralovics R, Skoda RC. Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders. Blood Reviews. 2005;19:1–13.
  2. Tefferi A, Gary GD. Oncogenes in myeloproliferative disorders. Cell Cycle. 2007;6(5):550–566.
  3. Fanny BM, Hajer M, Christophe D, et al. Expression level and differential JAK2-V617F–binding of the adaptor protein Lnk regulates JAK2-mediated signals in myeloproliferative neoplasms. Blood. 2009;116:5961–5971.
  4. Spivak JL. Polycythemia vera: Myths, mechanisms, and management. Blood. 2002;100(13): 4272–4290
  5. Aaron DV, Ross LL. Genetics of myeloproliferative neoplasms. The Cancer Journal. 2014; Volume 20, Number 1, January/February.
  6. Khurum HK, Montserrat B, L Rhoda M. Cancer therapeutics: Targeting the apoptotic pathway. Critical Reviews in Oncology/Hematology. 2014.
  7. Wong RS. Apoptosis in cancer: From pathogenesis to treatment. Wong Journal of Experimental & Clinical Cancer Research. 2011;30(87):1–14.
  8. Lena FK, Gisela WS, Heike D, et al. Polymorphisms in the apoptotic pathway gene BCL-2 and survival in small cell lung cancer. J Thorac Oncol. 2011;6:183–189.
  9. Irina B, Eva G, Wen-Yu C, et al. Analysis of single nucleotide polymorphisms in the FAS and CTLA-4 genes of peripheral T-cell lymphomas. J Hematopathol. 2008;1:11–21.
  10. Miller SA, Dykes DD, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.
  11. Wanlong M, Hagop K, Xi Z, et al. JAK2 Exon 14 Deletion in Patients with Chronic Myeloproliferative Neoplasms. PLoS One. 2010;5:1–7.
  12. Provan D, Gribben J. Molecular Haematology 2th Edition. UK. Blackwell Publishing 2005;P90.
  13. Farre L, Bittencourt AL, Silva-Santos G, et al. FAS 670 promotor polymorphism is associated to susceptibility clinical presentation, and survival in adult Tcell leukemia. J Leukocyte Biol. 2008;83:220–222.
  14. Hagen SB, Lukas CH, Klaus JS, et al. Regulatory BCL2 promoter polymorphism (2938C>A) is associated with adverse outcome in patients with prostate carcinoma. Int J Cancer. 2011;129:2390–2399.
  15. Ning Z, Xiaoyan L, Kai T, et al. BCL-2 (-938C > A) polymorphism is associated with breast cancer susceptibility. BMC Medical Genetics. 2011;12:48.
  16. Joon HM, Sang KS, Myung HL, et al. BCL2 gene polymorphism could predict the treatment outcomes in acute myeloid leukemia patients. Leukemia Research. 2010;166–172.
  17. Holger N, Ulrich HF, Maja B, et al. Association of a novel regulatory polymorphism (-938C>A) in the BCL2 gene promoter with disease progression and survival in chronic lymphocytic leukemia. Blood. 2007;290-297.
  18. Kim DH, Xu W, Ma C, et al. Genetic variants in the candidate genes of the apoptosis pathway and susceptibility to chronic myeloid leukemia. Blood. 2009;(113):11.
  19. Peng H, Aiello A, Packham G, Isaacson PG, Pan L. Infrequent bax gene mutations in B-cell lymphomas. J Pathol. 1998;186:378–382.
  20. Anurag S, Oksana M, Koravangattu S, Sathiyanarayanan V, David PS. Association of a novel single nucleotide polymorphism, G(2248)A, in the 50-UTR of BAX gene in chronic lymphocytic leukemia with disease progression and treatment resistance. Cancer Letters. 2002;187:199–205.
  21. Skogsberg A, Tobin G, Kröber A, et al. The G(-248)A polymorphism in the promoter region of the Bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukemia. Leukemia. 2006;20,77–81.