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The chimeric transcription factor TCF3-HLF defines an incurable acute lymphoblastic leukemia subtype. Here we decipher the regulome of endogenous TCF3-HLF and dissect its essential transcriptional components and targets by functional genomics. We demonstrate that TCF3-HLF recruits HLF binding sites at hematopoietic stem cell/myeloid lineage associated (super-) enhancers to drive lineage identity and self-renewal. Among direct targets, hijacking an HLF binding site in a MYC enhancer cluster by TCF3-HLF activates a conserved MYC-driven transformation program crucial for leukemia propagation in vivo. TCF3-HLF pioneers the cooperation with ERG and recruits histone acetyltransferase p300 (EP300), conferring susceptibility to EP300 inhibition. Our study provides a framework for targeting driving transcriptional dependencies in this fatal leukemia., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This round table discussion takes the diversity of discourse and practice shaping modern knowledge about childhood as an opportunity to engage with recent historiographical approaches in the history of science. It draws attention to symmetries and references among scientific, material, literary and artistic cultures and their respective forms of knowledge. The five participating scholars come from various fields in the humanities and social sciences and allude to historiographical and methodological questions through a range of examples. Topics include the emergence of children's rooms in US consumer magazines, research on the unborn in nineteenth-century sciences of development, the framing of autism in nascent child psychiatry, German literary discourses about the child's initiation into writing, and the sociopolitics of racial identity in the photographic depiction of African American infant corpses in the early twentieth century. Throughout the course of the paper, childhood emerges as a topic particularly amenable to interdisciplinary perspectives that take the history of science as part of a broader history of knowledge.