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Article Dans Une Revue Current Opinion in Oncology Année : 2021

Epigenetic focus on angioimmunoblastic T-cell lymphoma: pathogenesis and treatment.

Résumé

Purpose of review: Angioimmunoblastic T-cell lymphoma (AITL) is a frequent peripheral T-cell lymphoma affecting elderly patients with a poor outcome when treated with conventional chemotherapy. Molecular studies revealed a homogenous mutational landscape gathering anomalies in genes regulating the DNA methylation and hydroxymethylation and anomalies in T-cell signalling. Recent findings: Recent studies indicate that AITL emerges from a TET2 and/or DNMT3A mutated clonal haematopoiesis. This clonal haematopoiesis bearing mutations altering DNA hydroxymethylation can explain the observed coexistence of AITL with myeloid neoplasms. In addition, AITL development requires AITL-specific mutations, such as the RHOAG17V mutations. Combination of TET2 and RHOAG17V alterations results in the development of AITL-like disease in mouse models. The impact of the presence of these mutations on patient outcome seems limited and new biological factor predicting treatment response and survival remains to be determined. At the therapeutic level, therapies targeting epigenetic changes, such as histone deacetylase inhibitors and the hypomethylating 5-azacytidine agent, could have efficacy in this disease and gave promising results. Recent progress in mouse model development should allow development of new treatments. Summary: Epigenetic changes are frequent in AITL and could be a promising target.
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Dates et versions

hal-04205878 , version 1 (13-09-2023)

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Gamze Tari, François Lemonnier, Franck Morschhauser. Epigenetic focus on angioimmunoblastic T-cell lymphoma: pathogenesis and treatment.. Current Opinion in Oncology, 2021, Current Opinion in Oncology, ⟨10.1097/CCO.0000000000000773⟩. ⟨hal-04205878⟩

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