Chromatin hubs drive key regulatory networks in leukemia

Molecular Cell, Год журнала: 2025, Номер 85(1), С. 1 - 2

Опубликована: Янв. 1, 2025

Язык: Английский

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The common murine retroviral integration site activating Hhex marks a distal regulatory enhancer co-opted in human Early T-cell precursor leukemia

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108233 - 108233

Опубликована: Янв. 1, 2025

Язык: Английский

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Native stem cell transcriptional circuits define cardinal features of high-risk leukemia

The Journal of Experimental Medicine, Год журнала: 2025, Номер 222(4)

Опубликована: Фев. 19, 2025

While the mutational landscape across early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) and ETP-like is known, establishing a unified framework that activates stem cell genes characteristic of these tumors remains elusive. Using complementary mouse human models, chromatin mapping, enhancer profiling, we show coactivator ZMIZ1 promotes normal malignant ETP population growth by inducing transcription factor MYB in feedforward circuits to convergently activate oncogenes (MEF2C, MYCN, BCL2) through essential enhancers. A key superenhancer, N-Myc regulating (NMRE), drives but dispensable for lymphopoiesis. This network superenhancers identifies treatment-resistant poor survival outcomes; unifies diverse ETP-ALLs; contributes cardinal features recently genomically identified high-risk bone marrow progenitor-like (BMP-like) ETP-ALL tumor—stem cell/myeloid gene expression, inhibited NOTCH1-induced development, aggressive clinical behavior, venetoclax sensitivity. Since homeostasis, it might be possible safely target this treat diseases.

Язык: Английский

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Three-dimensional regulatory hubs support oncogenic programs in glioblastoma

Molecular Cell, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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