Low level CpG island promoter methylation predicts a poor outcome in adult T-cell acute lymphoblastic leukemia.
Haematologica
; 105(6): 1575-1581, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-31537687
ABSTRACT
Cancer cells undergo massive alterations in their DNA methylation patterns which result in aberrant gene expression and malignant phenotypes. Abnormal DNA methylation is a prognostic marker in several malignancies, but its potential prognostic significance in adult T-cell acute lymphoblastic leukemia (T-ALL) is poorly defined. Here, we performed methylated DNA immunoprecipitation to obtain a comprehensive genome-wide analysis of promoter methylation in adult T-ALL (n=24) compared to normal thymi (n=3). We identified a CpG hypermethylator phenotype that distinguishes two T-ALL subgroups and further validated it in an independent series of 17 T-lymphoblastic lymphoma. Next, we identified a methylation classifier based on nine promoters which accurately predict the methylation phenotype. This classifier was applied to an independent series of 168 primary adult T-ALL treated accordingly to the GRAALL03/05 trial using methylation-specific multiplex ligation-dependent probe amplification. Importantly hypomethylation correlated with specific oncogenic subtypes of T-ALL and identified patients associated with a poor clinical outcome. This methylation-specific multiplex ligation-dependent probe amplification based methylation profiling could be useful for therapeutic stratification of adult T-ALL in routine practice. The GRAALL-2003 and -2005 studies were registered at http//www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucemia-Linfoma Linfoblástico de Células Precursoras
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Leucemia-Linfoma Linfoblástico de Células T Precursoras
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article