Acute lymphoblastic leukemia(ALL)is the most common pediatric malignancy,occurring in approximately 25%of all childhood cancer cases,and it remains one of the most common causes of death from disease in childhood.Despite the large number of experimental agents available,the development of new drugs is highly limited by patient numbers and opportunities of clinical trials.Therefore,as part of the Pediatric Preclinical Testing Program,we have developed pediatric ALL patient-derived xenografts(PDXs)model to preclinically test new agents and prioritize them for entering clinical trails.Furthermore,glucocorticoids are critical components of combination chemotherapy regimens in pediatric ALL,but the emergence of resistance remains a significant barrier to cure.Recently,we found that glucocorticoid resistance is associated with inhibition of glucocorticoid receptor binding at a novel enhancer in the pro-apoptotic gene BIM.We also discovered an open chromatin conformation in this enhancer exclusively in lymphoid cells compared with cells of other histotypes,indicating a possible mechanism by which lymphoid cells are primed for glucocorticoid-induced apoptosis.Overall,this study has idenitified a novel epigenetic mechanism associated with glucocorticoid resistance of ALL.