Perfil de metilación de genes supresores de tumores como factor pronóstico en pacientes con leucemia mieloide aguda

Translated title of the contribution: Promoter methylation profile in tumor suppressor genes as prognosis factor in patients with acute myeloid leukemia

J. Soledad Reyes, M. Priscilla Brebi, G. Carmen Gloria Ili, N. Sergio Muñoz, A. Angélica Melo, P. Rafael Guerrero

Research output: Contribution to journalArticle

Abstract

There is growing evidence than acute myeloid leukemia presents a specific methylation profile. The Methylation of CpG islands within gene promoters is a major epigenetic transcriptional control mechanism and plays a critical role in the transcriptional silencing of tumor suppressor genes. This provides new insights into the biology of the disease and it may offer novel therapeutic opportunities. To identify the promoter methylation profile of tumor suppressor genes (p15, p16, ESR1, IGSF4, SOCS1, RARB y DAPK), and to relate the percentage of methylation with clinicopathological features, as age, gender, white cell count, disease classification and survival rates. Bone marrow and peripheral blood samples were collected at diagnosis from 33 patients with acute myeloid leukemia, infants and adult, between 1997 and 2008 from Hernán Henríquez Aravena Hospital, Temuco, Chile. Methylation in the promoter areas of each tumor suppressor gene was analyzed using the mehylation specific polymerase chain reaction (MSP) technique using sodium bisulfite modification. The frequency of hypermethylation among the patient samples was 88%, 27%, 27%, 21%, 15%, 3% and 0% for ESR1, RARb, IGSF4, p15, SOCS1, DAPK, and P16 for each one. Methylation was significantly associated with an inferior overall survival (p=0.03 and p=0.02). When both genes are used, inferior survival is even more significant (p=0.002). There is no significant correlation between methylation and clinicopathological features.Patients with AML have hipermetilation at the promoter region of some tumor supressor genes, with a negative effect in the overall survival. This could eventually become part of establishing a characteristical methilation pattern with clinical utility.

Original languageSpanish
Pages (from-to)151-157
Number of pages7
JournalInternational Journal of Morphology
Volume29
Issue number1
StatePublished - Mar 2011

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Keywords

  • Acute myeloid leukemia
  • Epigenetic
  • Methylation
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Anatomy

Cite this

Soledad Reyes, J., Priscilla Brebi, M., Carmen Gloria Ili, G., Sergio Muñoz, N., Angélica Melo, A., & Rafael Guerrero, P. (2011). Perfil de metilación de genes supresores de tumores como factor pronóstico en pacientes con leucemia mieloide aguda. International Journal of Morphology, 29(1), 151-157.