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.
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