Activated NOTCH1 is a common driver of T-cell acute lymphoblastic leukemia (T-ALL). Due to the toxicity of and resistance to NOTCH1 inhibitors, therapies targeting molecules downstream of NOTCH1 might help treat relapsed patients. In this study, Lancho et al. reveal that NOTCH1 directly activates SIRT1 transcription through a distal enhancer element. Genetic loss or inhibition of SIRT1 leads to significant antileukemic effects in mouse models with different SIRT1 allelic dosages. Mechanistically, the oncogenic effects of SIRT1 are mediated, at least in part, by its deacetylation and activation of KAT7. These results uncover the therapeutic potential of SIRT1-KAT7 axis inhibition in T-ALL. ■

See article, p. 12.

The regulatory targets of the ETS repressor ETV6, a candidate tumor suppressor in B-lymphoblastic leukemia (B-ALL), have remained poorly understood. Kodgule, Goldman, Monovich et al. show that ETV6 binds to genomic short tandem repeats of the sequence ‘GGAA’ that are repressed in normal...

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