DOI QR코드

DOI QR Code

Prognostic Value of a CYP2B6 Gene Polymorphism in Patients with Acute Myeloid Leukemia

  • Alazhary, Nevin M (Department of Clinical Pathology, National Cancer Institute, Cairo University) ;
  • Shafik, Roxan E (Department of Clinical Pathology, National Cancer Institute, Cairo University) ;
  • Shafik, Hanan E (Department of Medical Oncology, National Cancer Institute, Cairo University) ;
  • Kamel, Mahmoud M (Department of Clinical Pathology, National Cancer Institute, Cairo University)
  • Published : 2015.06.26

Abstract

Background: The objectives of this study aimed to detect a CYP2B6 polymorphism in de novo cases of acute myeloid leukemia patients and identify any role in disease progression and outcome. Materials and Methods: DNA was isolated from peripheral blood of 82 newly diagnosed acute myeloid leukemia cases and the CYP2B6 G15631T gene polymorphism was assayed by PCR restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of the GG genotype (wild type) was 48 (58.5%) and that of the mutant type T allele was 34 (41.9%). GT genotype heterozygous variants were found in 28 (34%), and TT genotype homozygous variants in 6 (7.3%) cases. We found no significant association between the CYP2B6 G15631T polymorphism and complete response (CR) (p-value=0.768), FAB classification (p-value=0.51), cytogenetic analysis (p-value=0.673), and overall survival (p-value=0.325). Also, there were no significant links with early toxic death (p-value=0.92) or progression-free survival (PFS) (p-value=0.245). Conclusions: Our results suggest that the CYP2B6 polymorphism has no role in disease progression, therapeutic outcome, patient free survival, early toxic death and overall survival in acute myeloid leukemia patients.

Keywords

CYP2B6 G15631T;AML;prognosis;PCR/RFLP

References

  1. Ali GT, Al-azhary NM, Mokhtar DA (2014). Frequency and prognostic significant of CYP3A4-A-290G polymorphism in acute myeloid leukemia, J Adv Res, 5, 657-61 https://doi.org/10.1016/j.jare.2013.10.002
  2. Anderson K, Lutz C, van Delft FW, et al (2011). Genetic variegation of clonal architecture and propagating cells in leukaemia. Nature, 469, 356-361. https://doi.org/10.1038/nature09650
  3. Berkoz M, Yalin S (2009). Association of CYP2B6 G15631T polymorphism with acute leukemia susceptibility. Leuk Res, 33, 919-23. https://doi.org/10.1016/j.leukres.2008.11.014
  4. Da Silva Silveira V, Canalle R, Scrideli CA, et al (2009). Polymorphisms of xenobiotic metabolizing enzymes and DNA repair genes and outcome in childhood acute lymphoblastic leukemia. Leuk Res, 33, 898-901. https://doi.org/10.1016/j.leukres.2008.12.006
  5. Daraki A, Zachaki S, Koromila T, et al (2014). The G516T CYP2B6 germline polymorphism affects the risk of acute myeloid leukemia and is associated with specific chromosomal abnormalities. PLoS ONE, 9, 88879. https://doi.org/10.1371/journal.pone.0088879
  6. Dunna NR, Vure S, Sailaja K, et al (2012). TP53 codon 72 polymorphism and risk of acute leukemia. Asian Pac J Cancer Prev, 13, 347-50. https://doi.org/10.7314/APJCP.2012.13.1.349
  7. Eyada TK, El Ghonemy EG, El Ghoroury EA, et al (2007). Study of genetic polymorphism of xenobiotic enzymes in acute leukemia. Blood Coagul Fibrinolysis, 18, 489-95. https://doi.org/10.1097/MBC.0b013e3281eec930
  8. Firoz Ahmad, Rupali Mohota, Savita Sanap, et al (2014). Molecular Evaluation of DNMT3A and IDH1/2 Gene Mutation: Frequency, Distribution Pattern and Associations with Additional Molecular Markers in Normal Karyotype Indian Acute Myeloid Leukemia Patients. Asian Pac J Cancer Prev, 15, 1247-53. https://doi.org/10.7314/APJCP.2014.15.3.1247
  9. Grimwade D, Mrozek K (2011). Diagnostic and prognostic value of cytogenetics in acute myeloid leukemia. Hematol Oncol Clin North Am, 25, 1135-61. https://doi.org/10.1016/j.hoc.2011.09.018
  10. Jamroziak K, Mlynarski W, Balcerczak E, et al (2004). Functional C3435T polymorphism of MDR1 gene: an impact on genetic susceptibility and clinical outcome of childhood acute lymphoblastic leukemia. Eur J Haematol, 72, 314-21. https://doi.org/10.1111/j.1600-0609.2004.00228.x
  11. Kayser S, Zucknick M, Dohner K, et al (2012). Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies. Blood, 119, 551-8. https://doi.org/10.1182/blood-2011-07-367508
  12. Lamba V, Lamba J, Yasuda K, et al (2003). Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression. J Pharmacol Exp Ther, 307, 906-22. https://doi.org/10.1124/jpet.103.054866
  13. Lapinski L1, Orzechowska-Juzwenko K, Wiela-Hojenska A, et al (2011). Influence of anticancer therapy on oxidation phenotype and acetylation phenotype in patients with acute myeloblastic leukemia. Pharmacol Rep, 63, 149-56. https://doi.org/10.1016/S1734-1140(11)70409-1
  14. Long Su, Xian Li, Su-Jun Gao, et al (2014). Cytogenetic and genetic mutation features of de novo acute myeloid leukemia in elderly Chinese patients. Asian Pac J Cancer Prev, 15, 895-8. https://doi.org/10.7314/APJCP.2014.15.2.895
  15. MT Voso, F D'Alo', D Gumiero, et al (2005). The CYP1A1*2a allele is an independent prognostic factor for acute myeloid leukemia. Haematologica, 90, 982-4.
  16. Nageswararao D, Manjula G, Sailaja K, et al (2010). Association of CYP2D6*4 polymorphism with acute leukemia. J Cell Tissue Res, 10, 2201-5.
  17. Palodetto B, de Melo Campos P, Benites BD, et al (2013). MDR- 1 and GST polymorphisms are involved in myelodysplasia progression. Leuk Res, 37, 970-3. https://doi.org/10.1016/j.leukres.2013.04.024
  18. Ruan XL1, Li S, Zeng XT, et al (2013). No association between cytochrome P450 2D6 gene polymorphism and risk of acute leukemia: evidence based on a meta-analysis. Chin Med J (Engl), 126, 3750-3.
  19. Shimada T (2006). Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic hydrocarbons. Drug Metab Pharmacokinet, 21, 257-76. https://doi.org/10.2133/dmpk.21.257
  20. Simon Blechman Zeichner, Sarah Alghamdi, Gina Elhammady, et al (2014). Prognostic Significance of TP53 Mutations and Single Nucleotide Polymorphisms in Acute Myeloid Leukemia: A case Series and Literature Review. Asian Pac J Cancer Prev, 15, 1603-9. https://doi.org/10.7314/APJCP.2014.15.4.1603
  21. Turpeinen M, Zanger UM (2012). Cytochrome P450 2B6: function, genetics, and clinical relevance. Drug Metab Drug Inter, 27, 185-97.
  22. Xu C, Ogburn ET, Guo Y, Desta Z (2012). Effects of the CYP2B6*6 allele on catalytic properties and inhibition of CYP2B6 in vitro: implication for the mechanism of reduced efavirenz metabolism and other CYP2B6 substrates in vivo. Drug Metab Dispos, 40, 717-25. https://doi.org/10.1124/dmd.111.042416
  23. Yuan ZH, Liu Q, Zhang Y, et al (2011). CYP2B6 gene single nucleotide polymorphisms and leukemia susceptibility. Ann Hematol, 90, 293-9. https://doi.org/10.1007/s00277-010-1085-z
  24. Zanger UM, Klein K, Saussele T, et al (2007). Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance. Pharmacogenomics, 8, 743-59. https://doi.org/10.2217/14622416.8.7.743