Inhibiting H3K27 Demethylases Downregulates CREB-CREBBP, Overcoming Resistance in Relapsed Acute Lymphoblastic Leukemia.

ABSTRACT:

Background

CREB binding protein (CREBBP) is a key epigenetic regulator, altered in a fifth of relapsed cases of acute lymphoblastic leukemia (ALL). Selectively targeting epigenetic signaling may be an effective novel therapeutic approach to overcome drug resistance. Anti-tumor effects have previously been demonstrated for GSK-J4, a selective H3K27 histone demethylase inhibitor, in several animal models of cancers.

Methods

To characterize the effect of GSK-J4, drug response profiling, CRISPR-Dropout Screening, BH3 profiling and immunoblotting were carried out in ALL cell lines or patient derived samples.

Results

Here we provide evidence that GSK-J4 downregulates cyclic AMP-responsive element-binding protein (CREB) and CREBBP in B-cell precursor-ALL cell lines and patie

SUBMITTER: Lazaro-Navarro J 

PROVIDER: S-EPMC11719120 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature