3D Chromatin Remodeling in B-cell Development and B-cell Acute Lymphoblastic Leukemia [ChIP-seq]

Several studies have also shown changes in epigenetic landscape including differences across B-ALL subtypes. However, the state of the 3D genome across subtypes and how they compare to healthy B-cell progenitors remains unexplored.

Here we use Hi-C and RNA-seq to profile early B-cell progenitors from healthy donors and a number of B-ALL samples harboring the most frequent and prognostic structural variations, including KMT2A::AFF1 and BCR::ABL. We show that B-ALLs undergo subtype-specific changes in 3D genome organization that indicate the differentiation stage of the disease. Additional analysis shows B-ALLs acquire aberrant chromatin configurations and expression of oncogenic drivers compared to normal progenitors.