Impact of clinical features, cytogenetics, genetic mutations, and methylation dynamics of CDKN2B and DLC-1 promoters on treatment response to azacitidine.
Ann Hematol
; 99(3): 527-537, 2020 Mar.
Article
em En
| MEDLINE
| ID: mdl-31989250
ABSTRACT
Azacitidine (AZA) is a DNA hypomethylation agent administered in myeloid neoplasms; however, there is still a lack of established predictors of response. We studied 113 patients with myelodysplastic syndromes (n = 85) or acute myeloid leukemia (n = 28) who received AZA to assess the predictive value on response of clinical features, cytogenetics, and molecular markers. Overall, 46 patients (41%) responded to AZA. Platelet doubling after the first AZA cycle was associated with a better response (68% vs. 32% responders, P = 0.041). Co-occurrence of chromosome 7 abnormalities and 17p deletion was associated with a worse response (P = 0.039). Pre-treatment genetic mutations were detected in 98 patients (87%) and methylation of CDKN2B and DLC-1 promoters were detected in 50 (44%) and 37 patients (33%), respectively. Patients with SF3B1 mutations showed a better response to AZA (68% vs. 35% responders, P = 0.008). In contrast, subjects with mutations in transcription factors (RUNX1, SETBP1, NPM1) showed a worse response (20% vs. 47% responders, P = 0.014). DLC-1 methylation pre-treatment was associated with poor clinical features and its reduction post-treatment resulted in a better response to AZA in MDS patients (P = 0.037). In conclusion, we have identified several predictors of response to AZA that could help select the best candidates for this treatment.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Azacitidina
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Síndromes Mielodisplásicas
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DNA de Neoplasias
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Regiões Promotoras Genéticas
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Metilação de DNA
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Proteínas Ativadoras de GTPase
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Proteínas Supressoras de Tumor
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Inibidor de Quinase Dependente de Ciclina p15
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article