By identifying genes that influence sensitivity to GC-induced cell death, we found that histone methyltransferases G9a and G9a-like protein (GLP), two glucocorticoid receptor (GR) coactivators, are required for GC-induced cell death in acute lymphoblastic leukemia (B-ALL) cell line Nalm6.
Splicing variant profiles and single nucleotide polymorphisms of the glucocorticoid receptor gene in relation to glucocorticoid sensitivity of B-cell precursor acute lymphoblastic leukaemia.
Glucocorticoid receptor cooperated with CTCF at these LSOs to mediate DNA looping, which was inhibited by increased DNA methylation in glucocorticoid-resistant ALL and non-lymphoid cell types.
Importantly, we validated that miR-124, targeted and decreased the expression of glucocorticoid receptor (NR3C1), prevented the inhibitory effect of GC in ALL.
Glucocorticoids (GCs) and topoisomerase II inhibitors are used to treat acute lymphoblastic leukaemia (ALL) as they induce death in lymphoid cells through the glucocorticoid receptor (GR) and p53 respectively.
We use MARCoNI to determine the GR coregulator profile of glucocorticoid-sensitive (MM and ALL) and glucocorticoid-resistant (ALL) cells, and identify common and unique coregulators for different cell line comparisons.
Our results suggest that specific inhibition of the AKT1/14-3-3 activity on the cytoplasmic retention of GR may be a promising target for treating glucocorticoid resistance observed in ALL.
We investigated whether an altered individual glucocorticoid sensitivity due to particular glucocorticoid receptor single-nucleotide polymorphisms (SNPs) (N363S, ER22/23EK, and Bcl-1) influences the susceptibility to steroid-related toxicities, prognostic factors, and survival rates in children with acute lymphoblastic leukemia.
Loss of TBL1XR1 disrupts glucocorticoid receptor recruitment to chromatin and results in glucocorticoid resistance in a B-lymphoblastic leukemia model.
We delineated the transcriptional response to GC on the exon level in a time-resolved manner in a precursor B- and a T childhood ALL model employing Exon microarrays and combined this with genome-wide NR3C1-binding site detection using chromatin immunoprecipitation-on-chip technology.
This study aimed to determine if a facile assay of GR transcript levels might be promising for stratifying ALL patients into hormone-sensitive and hormone-resistant populations.
Evaluating the effect of 3 glucocorticoid receptor gene polymorphisms on risk of relapse in 100 Iranian children with acute lymphoblastic leukemia: a case-control study.
Further characterization of this complex as part of the GR regulatory circuitry could offer novel opportunities for improving the efficacy of GC-based therapies in ALL and other hematologic malignancies.
While the same level of GR is required to trigger apoptosis in both T-cell and pre-B-cell ALL lineages, similarities and differences were observed for the regulation of target genes in these lineages.
Cell lines cultured in high GC concentrations typically contain mutated glucocorticoid receptor (GR), something that is rarely found in primary ALL specimens.
However, we report the second case of ALL with a somatic mutation of the GR involving a 29-bp deletion in exon 8 and resulting in a truncated protein with loss of part of the ligand-binding domain.
Differential mRNA expression of glucocorticoid receptor alpha and beta is associated with glucocorticoid sensitivity of acute lymphoblastic leukemia in children.
Towards this aim we analyzed the CYP3A4-290A/G substitution and three NR3C1 polymorphisms (200G/A, 1220A/G and BclI RFLP) in 222 children with acute lymphoblastic leukemia (ALL) whose treatment protocols, among other components, contained corticosteroid drugs.
Therefore, we conclude that the expression of hsp90, the major component of the GR activating complex, is of minor importance for the in vivo GC resistance in childhood ALL.
These results provide the first evidence for somatic mutation in the hGR gene of a patient with acute lymphoblastic leukemia, offer a potential in vivo mechanism for acquisition of steroid resistance in leukemia, and suggest that screening for additional in vivo mutations will require analysis of genomic DNA.