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  • Traitements systémiques : découverte et développement

  • Leucémie

Recent progress toward epigenetic therapies: the example of mixed lineage leukemia

A partir des travaux récents sur les leucémies avec réarrangements MLL, cet article passe en revue les perspectives offertes par les connaissances sur des mécanismes épigénétiques pour développer des traitements anticancéreux

The importance of epigenetic gene regulatory mechanisms in normal and cancer development is increasingly evident. Genome-wide analyses have revealed the mutation, deletion and dysregulated expression of chromatin-modifying enzymes in a number of cancers, including hematologic malignancies. Genome-wide studies of DNA-methylation and histone modifications are beginning to reveal the landscape of cancer-specific chromatin patterns. In parallel, recent genetic loss-of-function studies in murine models are demonstrating functional involvement of chromatin-modifying enzymes in malignant cell proliferation and self-renewal. Paradoxically, the same chromatin modifiers can, depending on cancer type, be either hyperactive or inactivated in cancer. Increasingly, crosstalk between epigenetic pathways is being identified. Leukemias carrying MLL-rearrangements are quintessential cancers driven by dysregulated epigenetic mechanisms where fusion proteins containing N-terminal sequences of MLL require few or perhaps no additional mutations to cause human leukemia. Here we review how recent progress in the field of epigenetics opens potential mechanism-based therapeutic avenues.

Blood

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