Methylation Profile of Von Hipple Lindau Gene Promoter in Acute Lymphoblastic Leukemia Patients

  • Samaneh Ahmadi Department of Hematology, Faculty of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Shaban Alizadeh Department of Hematology, Faculty of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Fatemeh Nadali Department of Hematology, Faculty of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Sasan Ghaffari Department of Hematology, Faculty of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Mehdi Azad Department of Medical laboratory sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
Keywords: Acute Lymphoblastic Leukemia, von Hippel-Lindau Gene, DNA Methylation, Epigenetics

Abstract

Background: DNA methylation is an epigenetic mechanism that often modifies the function of genes and affects gene expression, which may sometimes lead to cancerdevelopment. Tumor suppressor genes such as VHL (Von Hippel-Lindau) may besilenced when affected by epigenetic alteration. This study investigated the DNAmethylation of VHL gene in ALL (Acute Lymphoblastic Leukemia) patients withmethylation specific PCR (MSP). Methods: The DNA of peripheral blood and bone marrow cells of 26 ALL patientsand 26 healthy control subjects were extracted, treated with bisulfite, and VHL genemethylation was subsequently analyzed using the MSP technique.Results: None of the patients showed signs of methylation in the VHL gene. Conclusion: Due to the lack of methylation in the VHL gene promoter in patientsand in the healthy control group, it is unlikely that the methylation of this gene canbe used in the diagnosis and prognosis of ALL patients.

References

Rodak BF, Fritsma GA, Keohane EM, Hematology: Clinical Principles and Applications. Amsterdam etherlands:BernadetteRodak; 2012.

Figueroa ME, Chen SC, Andersson AK, Phillips LA, Li Y,Sotzen J, et al. Integrated genetic and epigenetic analysisof childhood acute lymphoblastic leukemia. J Clin Invest2013;123:3099-111.

Agirre X, Vizmanos JL, Calasanz MJ, García-Delgado M,Larráyoz MJ, Novo FJ. Methylation of CpG dinucleotidesand/or CCWGG motifs at the promoter of TP53 correlateswith decreased gene expression in a subset of acute lymphoblasticleukemia patients. Oncogene 2003;22:1070.

Mehdipour P, Santoro F, Minucci S. Epigenetic alterations inacute myeloid leukemia. FEBS J 2015;282:1786-800.

Hendrich B, Bird A. Identification and characterization ofa family of mammalian methyl-CpG binding proteins. MolCell Biol 1998;18:6538-47

Saito Y, Jones PM. Epigenetic activation of tumor suppressormicroRNAs in human cancer cells. Cell cycle 2006;5:2220-2.

Banks RE, Tirukonda P, Taylor C, Hornigold N, AstutiD, Cohen D, et al. Genetic and epigenetic analysis of vonHippel-Lindau (VHL) gene alterations and relationshipwith clinical variables in sporadic renal cancer. Cancer Res2006;66:2000-11.

Morris MR, Maher ER. Epigenetics of renal cell carcinoma:the path towards new diagnostics and therapeutics. GenomeMed 2010;2:59.

Kim WY, Kaelin WG. Role of VHL gene mutation inhuman cancer. Journal of clinical oncology. 2004 Dec 15;22(24):4991-5004.

Azad M, Biniaz RB, Goudarzi M, Mobarra N, Alizadeh S,Nasiri H, et al. Short View of Leukemia Diagnosis and Treatmentin Iran. Int J Hematol Oncol Stem Cell Res 2015;9:88.

Garcia-Manero G, Yang H, Kuang SQ, O’Brien S, ThomasD, Kantarjian H. Epigenetics of acute lymphocytic leukemia.Semin Hematol 2009;46:24-32.

Corcoran M, Parker A, Orchard J, Davis Z, Wirtz M, SchmitzOJ, et al. ZAP-70 methylation status is associated with ZAP70 expression status in chronic lymphocytic leukemia. Haematologica2005;90:1078-88.

Hatzimichael E, Dranitsaris G, Dasoula A, Benetatos L,Stebbing J, Crook T, Bourantas KL. von Hippel–Lindaumethylation status in patients with multiple myeloma: a potentialpredictive factor for the development of bone disease.Clinical Lymphoma and Myeloma. 2009 Jun 1;9(3):239-42.

Azad M, Kaviani S, Noruzinia M, Mortazavi Y, Mobarra N,Alizadeh S, et al. Gene Expression Status and MethylationPattern in Promoter of P15INK4b and P16INK4a in CordBlood CD34+ Stem Cells. Iran J Basic Med Sci 2013;16:822.

Published
2018-05-14
How to Cite
1.
Ahmadi S, Alizadeh S, Nadali F, Ghaffari S, Azad M. Methylation Profile of Von Hipple Lindau Gene Promoter in Acute Lymphoblastic Leukemia Patients. BCCR. 10(2):49-3.
Section
Brief Communications