Low level CpG island promoter methylation predicts a poor outcome in adult T-cell acute lymphoblastic leukemia.
(2020) Haematologica — Vol. 105, n° 6, p. 1575-1581 (2020)
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- 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 specific oncogenic subtypes of T-cell Acute Lymphoblastic Leukemias 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-cell Acute Lymphoblastic Leukemias in routine practice. The GRAALL-2003 and -2005 studies were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively.
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Touzart, A., Boissel, N., Belhocine, M., Smith, C., Graux, C., Latiri, M., Lhermitte, L., Mathieu, E.-L., Huguet, F., Lamant, L., Ferrier, P., Ifrah, N., Macintyre, E., Dombret, H., Asnafi, V., & Spicuglia, S. (2020). Low level CpG island promoter methylation predicts a poor outcome in adult T-cell acute lymphoblastic leukemia. Haematologica, 105(6), 1575-1581. https://doi.org/10.3324/haematol.2019.223677 (Original work published 2020)