PU.1 eviction at lymphocyte-specific chromatin domains mediates glucocorticoid response in acute lymphoblastic leukemia.

ABSTRACT: The epigenetic landscape plays a critical role in cancer progression, yet its therapeutic potential remains underexplored. Glucocorticoids are essential components of treatments for lymphoid cancers, but resistance, driven in part by epigenetic changes at glucocorticoid-response elements, poses a major challenge to effective therapies. Here we show that glucocorticoid treatment induces distinct patterns of chromosomal organization in glucocorticoid-sensitive and resistant acute lymphoblastic leukemia xenograft models. These glucocorticoid-response elements are primed by the pioneer transcription factor PU.1, which interacts with the glucocorticoid receptor. Eviction of PU.1 promotes receptor binding, increasing the expression of genes involved in apoptosis and facilitating a stronger thera

SUBMITTER: Beck D 

PROVIDER: S-EPMC11549222 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature