title: Prognostic impact of the number of methylated genes in myelodysplastic syndromes and acute myeloid leukemias treated with azacytidine.
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.
authors.affiliation: Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Abáigar
authors.forename: Fernando
authors.initials: F
authors.lastname: Ramos
authors.forename: Rocío
authors.initials: R
authors.lastname: Benito
authors.forename: María
authors.initials: M
authors.lastname: Díez-Campelo
authors.forename: Javier
authors.initials: J
authors.lastname: Sánchez-del-Real
authors.forename: Lourdes
authors.initials: L
authors.lastname: Hermosín
authors.forename: Juan Nicolás
authors.initials: JN
authors.lastname: Rodríguez
authors.forename: Carlos
authors.initials: C
authors.lastname: Aguilar
authors.forename: Isabel
authors.initials: I
authors.lastname: Recio
authors.forename: Jose María
authors.initials: JM
authors.lastname: Alonso
authors.forename: Natalia
authors.initials: N
authors.lastname: de las Heras
authors.forename: Marta
authors.initials: M
authors.lastname: Megido
authors.forename: Marta
authors.initials: M
authors.lastname: Fuertes
authors.forename: María Consuelo
authors.initials: MC
authors.lastname: del Cañizo
authors.forename: Jesús María
authors.initials: JM
authors.lastname: Hernández-Rivas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D020732:Cytogenetic Analysis / Q000379:methods; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine