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01.11.2013 | Original Article

Prognostic impact of the number of methylated genes in myelodysplastic syndromes and acute myeloid leukemias treated with azacytidine

verfasst von: María Abáigar, Fernando Ramos, Rocío Benito, María Díez-Campelo, Javier Sánchez-del-Real, Lourdes Hermosín, Juan Nicolás Rodríguez, Carlos Aguilar, Isabel Recio, Jose María Alonso, Natalia de las Heras, Marta Megido, Marta Fuertes, María Consuelo del Cañizo, Jesús María Hernández-Rivas

Erschienen in: Annals of Hematology | Ausgabe 11/2013

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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.

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Titel: Prognostic impact of the number of methylated genes in myelodysplastic syndromes and acute myeloid leukemias treated with azacytidine
verfasst von: María Abáigar
Fernando Ramos
Rocío Benito
María Díez-Campelo
Javier Sánchez-del-Real
Lourdes Hermosín
Juan Nicolás Rodríguez
Carlos Aguilar
Isabel Recio
Jose María Alonso
Natalia de las Heras
Marta Megido
Marta Fuertes
María Consuelo del Cañizo
Jesús María Hernández-Rivas
Publikationsdatum: 01.11.2013
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 11/2013
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-013-1799-9

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Prognostic impact of the number of methylated genes in myelodysplastic syndromes and acute myeloid leukemias treated with azacytidine

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