Low level CpG island promoter methylation predicts a poor outcome in adult T-cell acute lymphoblastic leukemia.

Low level CpG island promoter methylation predicts a poor outcome in adult T-cell acute lymphoblastic leukemia. Haematologica. 2019 Sep 19;: Authors: Touzart A, Boissel N, Belhocine M, Smith C, Graux C, Latiri M, Lhermitte L, Mathieu EL, Huguet F, Lamant L, Ferrier P, Ifrah N, Macintyre E, Dombret H, Asnafi V, Spicuglia S 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 is poorly defined. Here, we performed methylated DNA immunoprecipitation to obtain a comprehensive genome-wide analysis of promoter methylation in adult T-cell Acute Lymphoblastic Leukemia (n=24) compared to normal thymi (n=3). We identified a CpG hypermethylator phenotype that distinguishes two T-cell acute lymphoblastic leukemia subgroups and further validate it in an independent series of 17 T-Lymphoblastic Lymphoma. Next, we identified a methylation classifier based on 9 promoters which accurately predict the methylation phenotype. This classifier was applied to an independent series of 168 primary adult T-cell Acute Lymphoblastic Leukemias treated accordingly to the GRAALL03/05 trial using methylation-specific multiplex ligation-dependent probe amplification. Importantly hypomethylation correlated with spe...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research