The ETO2 transcriptional cofactor maintains acute leukemia by driving a MYB/EP300-dependent stemness program

Transcriptional cofactors of the ETO family are recurrent fusion partners in acute leukemia. We characterized the ETO2 regulome by integrating transcriptomic and chromatin binding analyses in human erythroleukemia xenografts and controlled ETO2 depletion models. We demonstrate that beyond its well-established repressive activity, ETO2 directly activates transcription of MYB, among other genes.

Citation:
Fagnan A, Aid Z, Baille M, Drakul A, ……. Malinge S, Wichmann C, et al. The ETO2 transcriptional cofactor maintains acute leukemia by driving a MYB/EP300-dependent stemness program. HemaSphere. 2024;8(6).

Keywords:
Leukemia; children's cancers; chromatin

Abstract:
Transcriptional cofactors of the ETO family are recurrent fusion partners in acute leukemia. We characterized the ETO2 regulome by integrating transcriptomic and chromatin binding analyses in human erythroleukemia xenografts and controlled ETO2 depletion models. We demonstrate that beyond its well-established repressive activity, ETO2 directly activates transcription of MYB, among other genes.