A facile, branched DNA assay to quantitatively measure glucocorticoid receptor auto-regulation in T-cell acute lymphoblastic leukemia.
- Author:
Jason R SCHWARTZ
1
;
Purvaba J SARVAIYA
;
Lily E LEIVA
;
Maria C VELEZ
;
Tammuella C SINGLETON
;
Lolie C YU
;
Wayne V VEDECKIS
Author Information
- Publication Type:Journal Article
- MeSH: Adolescent; Antineoplastic Agents, Hormonal; pharmacology; Apoptosis; drug effects; Branched DNA Signal Amplification Assay; methods; Cell Line, Tumor; Child; Dexamethasone; pharmacology; Drug Resistance, Neoplasm; Exons; Glucocorticoids; pharmacology; Humans; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; metabolism; pathology; Receptors, Glucocorticoid; genetics; metabolism; Reverse Transcriptase Polymerase Chain Reaction; methods; Transcription, Genetic; drug effects; Up-Regulation
- From:Chinese Journal of Cancer 2012;31(8):381-391
- CountryChina
- Language:English
- Abstract: Glucocorticoid (GC) steroid hormones are used to treat acute lymphoblastic leukemia (ALL) because of their pro-apoptotic effects in hematopoietic cells. However, not all leukemia cells are sensitive to GC, and no assay to stratify patients is available. In the GC-sensitive T-cell ALL cell line CEM-C7, auto-up-regulation of RNA transcripts for the glucocorticoid receptor (GR) correlates with increased apoptotic response. 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. The GR transcript profiles of various lymphoid cell lines and 4 bone marrow samples from patients with T-cell ALL were analyzed using both an optimized branched DNA (bDNA) assay and a real-time quantitative reverse transcription-polymerase chain reaction assay. There were significant correlations between both assay platforms when measuring total GR (exon 5/6) transcripts in various cell lines and patient samples, but not for a probe set that detects a specific, low abundance GR transcript (exon 1A3). Our results suggest that the bDNA platform is reproducible and precise when measuring total GR transcripts and, with further development, may ultimately offer a simple clinical assay to aid in the prediction of GC-sensitivity in ALL patients.
