Asian Pacific Journal of Cancer Prevention

  • 제15권1호
  • /
  • Pages.75-84
  • /
  • 2014
  • /
  • 1513-7368(pISSN)
  • /
  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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DNA Hypermethylation of Cell Cycle (p15 and p16) and Apoptotic (p14, p53, DAPK and TMS1) Genes in Peripheral Blood of Leukemia Patients

  • Bodoor, Khaldon (Department of Biology, Jordan University of Science and Technology) ;
  • Haddad, Yazan (Department of Biology, Jordan University of Science and Technology) ;
  • Alkhateeb, Asem (Department of Biology, Jordan University of Science and Technology) ;
  • Al-Abbadi, Abdullah (Department of Hematology and Oncology, University of Jordan) ;
  • Dowairi, Mohammad (Department of Hematology and Oncology, University of Jordan) ;
  • Magableh, Ahmad (Department of Hematology and Oncology, University of Jordan) ;
  • Bsoul, Nazzal (Department of Hematology and Oncology, University of Jordan) ;
  • Ghabkari, Abdulhameed (Department of Biology, Jordan University of Science and Technology)
  • 발행 : 2014.01.15
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Aberrant DNA methylation of tumor suppressor genes has been reported in all major types of leukemia with potential involvement in the inactivation of regulatory cell cycle and apoptosis genes. However, most of the previous reports did not show the extent of concurrent methylation of multiple genes in the four leukemia types. Here, we analyzed six key genes (p14, p15, p16, p53, DAPK and TMS1) for DNA methylation using methylation specific PCR to analyze peripheral blood of 78 leukemia patients (24 CML, 25 CLL, 12 AML, and 17 ALL) and 24 healthy volunteers. In CML, methylation was detected for p15 (11%), p16 (9%), p53 (23%) and DAPK (23%), in CLL, p14 (25%), p15 (19%), p16 (12%), p53 (17%) and DAPK (36%), in AML, p14 (8%), p15 (45%), p53 (9%) and DAPK (17%) and in ALL, p15 (14%), p16 (8%), and p53 (8%). This study highlighted an essential role of DAPK methylation in chronic leukemia in contrast to p15 methylation in the acute cases, whereas TMS1 hypermethylation was absent in all cases. Furthermore, hypermethylation of multiple genes per patient was observed, with obvious selectiveness in the 9p21 chromosomal region genes (p14, p15 and p16). Interestingly, methylation of p15 increased the risk of methylation in p53, and vice versa, by five folds (p=0.03) indicating possible synergistic epigenetic disruption of different phases of the cell cycle or between the cell cycle and apoptosis. The investigation of multiple relationships between methylated genes might shed light on tumor specific inactivation of the cell cycle and apoptotic pathways.

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참고문헌

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  9. 5-Azacitidine induces demethylation of PTPL1 and inhibits growth in non-Hodgkin lymphoma vol.36, pp.3, 2015, https://doi.org/10.3892/ijmm.2015.2269
  10. Hypermethylation of p15 gene associated with an inferior poor long-term outcome in childhood acute lymphoblastic leukemia vol.142, pp.2, 2016, https://doi.org/10.1007/s00432-015-2063-6
  11. Decreased expression of p27 is associated with malignant transformation and extrathyroidal extension in papillary thyroid carcinoma vol.37, pp.3, 2016, https://doi.org/10.1007/s13277-015-4163-y
  12. DNA methylation and leukemia susceptibility in China: Evidence from an updated meta-analysis vol.5, pp.3, 2016, https://doi.org/10.3892/mco.2016.959
  13. SMG1 Acts as a Novel Potential Tumor Suppressor with Epigenetic Inactivation in Acute Myeloid Leukemia vol.15, pp.9, 2014, https://doi.org/10.3390/ijms150917065
  14. Silencing of LSD1 gene modulates histone methylation and acetylation and induces the apoptosis of JeKo-1 and MOLT-4 cells vol.40, pp.2, 2017, https://doi.org/10.3892/ijmm.2017.3032
  15. Regulation of Cancer Stem Cell Metabolism by Secreted Frizzled-Related Protein 4 (sFRP4) vol.10, pp.2, 2018, https://doi.org/10.3390/cancers10020040
  16. Aberrant DNA Methylation in Chronic Myeloid Leukemia: Cell Fate Control, Prognosis, and Therapeutic Response vol.56, pp.3, 2018, https://doi.org/10.1007/s10528-018-9841-1