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

• Published in: Annals of hematology Vol. 92; no. 11; pp. 1543 - 1552
• Main Authors: Abáigar, María, Ramos, Fernando, Benito, Rocío, Díez-Campelo, María, Sánchez-del-Real, Javier, Hermosín, Lourdes, Rodríguez, Juan Nicolás, Aguilar, Carlos, Recio, Isabel, Alonso, Jose María, de las Heras, Natalia, Megido, Marta, Fuertes, Marta, del Cañizo, María Consuelo, Hernández-Rivas, Jesús María
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-11-2013; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - therapeutic use; Azacitidine - therapeutic use; Cytogenetic Analysis - methods; DNA Methylation - drug effects; DNA Methylation - genetics; Female; Hematology; Humans; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Male; Medicine; Medicine & Public Health; Middle Aged; Myelodysplastic syndromes; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - mortality; Oncology; Original Article; Prognosis; Survival Rate - trends; Treatment Outcome; Azacytidine; Methylation; Acute myeloid leukemia; Survival; Myelodysplastic syndromes
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-013-1799-9

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.