Three-dimensional chromatin landscapes in MLLr AML

Pinpin Sui, Zhihong Wang, Peng Zhang, Feng Pan

Producción científica: Letterrevisión exhaustiva


Rearrangements of the mixed lineage leukemia (MLLr) gene are frequently associated with aggressive acute myeloid leukemia (AML). However, the treatment options are limited due to the genomic complexity and dynamics of 3D structure, which regulate oncogene transcription and leukemia development. Here, we carried out an integrative analysis of 3D genome structure, chromatin accessibility, and gene expression in gene-edited MLL-AF9 AML samples. Our data revealed profound MLLr-specific alterations of chromatin accessibility, A/B compartments, topologically associating domains (TAD), and chromatin loops in AML. The local 3D configuration of the AML genome was rewired specifically at loci associated with AML-specific gene expression. Together, we demonstrate that MLL-AF9 fusion disrupts the 3D chromatin landscape, potentially contributing to the dramatic transcriptome remodeling in MLLr AML.

Idioma originalEnglish (US)
Número de artículo56
PublicaciónExperimental Hematology and Oncology
EstadoPublished - dic 2024

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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