Prognostic impact of the number of methylated genes in myelodysplastic syndromes and acute myeloid leukemias treated with azacytidine.
Ann Hematol
; 92(11): 1543-52, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23740492
ABSTRACT
The prognostic impact of the aberrant hypermethylation in response to azacytidine (AZA) remains to be determined. Therefore, we have analyzed the influence of the methylation status prior to AZA treatment on the overall survival and clinical response of myeloid malignancies. DNA methylation status of 24 tumor suppressor genes was analyzed by methylation-specific multiplex ligation-dependent probe amplification in 63 patients with myelodysplastic syndromes and acute myeloid leukemia treated with azacytidine. Most patients (73 %) showed methylation of at least one gene, but only 12 % of patients displayed ≥3 methylated genes. The multivariate analysis demonstrated that the presence of a high number (≥2) of methylated genes (P = 0.022), a high WBC count (P = 0.033), or anemia (P = 0.029) were independent prognostic factors associated with shorter overall survival. The aberrant methylation status did not correlate with the response to AZA, although four of the five patients with ≥3 methylated genes did not respond. By contrast, favorable cytogenetics independently influenced the clinical response to AZA as 64.7 % of patients with good-risk cytogenetic abnormalities responded (P = 0.03). Aberrant methylation status influences the survival of patients treated with AZA, being shorter in those patients with a high number of methylated genes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Azacitidina
/
Síndromes Mielodisplásicas
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Leucemia Mieloide Aguda
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Metilação de DNA
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Antimetabólitos Antineoplásicos
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Ann Hematol
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Espanha