Low Glucocorticoid Receptor α/β Ratio in T-cell Lymphoblastic Leukemia
| Autor: | D. E. Cole, Osmar Monte, P. C. Adamson, Carlos Alberto Longui, Alessandra Vottero, Tomoshige Kino, George P. Chrousos |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism T cell Blotting Western Clinical Biochemistry Biochemistry Receptors Glucocorticoid Endocrinology Glucocorticoid Sensitivity Glucocorticoid receptor Immunophenotyping Internal medicine medicine Humans Leukemia-Lymphoma Adult T-Cell Child Receptor Cell growth Chemistry Lymphoblast Biochemistry (medical) General Medicine Phenotype medicine.anatomical_structure Child Preschool Female Glucocorticoid medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1439-4286 0018-5043 |
| DOI: | 10.1055/s-2007-978661 |
| Popis: | Glucocorticoid therapy is pivotal in the treatment of acute lymphoblastic leukemia (ALL); it reduces cell proliferation, promotes cell cycle arrest, and induces cell death by apoptosis. The sensitivity of leukemic cells to glucocorticoids was previously related to the cell concentration of 3[H]dexamethasone-binding sites. The latter represents the classic glucocorticoid receptor (GR) isoform alpha that binds ligand and modulates the transcription rates of glucocorticoid-responsive genes. In ALL, lymphoblasts of T-lineage are less sensitive to glucocorticoids than cells of the B-lineage. The alternatively spliced GR isoform (GRP), which exerts a dominant negative effect on GRalpha-mediated transcriptional activity, has been proposed as a possible mediator of glucocorticoid resistance. In this study, we determined the amount of GRalpha and GRbeta in mononuclear cells from 13 newly diagnosed and untreated children with ALL and 9 controls by quantitative Western analysis. Generally, leukemic patients expressed 6 times less GRalpha (ALL= 0.54 +/- 1.1; controls = 3.1 +/- 0.9; p < 0.01) than controls, but the same amount of GRbeta (ALL=3.62 +/- 3.3; controls = 3.6 +/- 3.4). ALL patients with T-cell disease had a much lower GRalpha (0.09 +/- 0.1; p < 0.01) but a similar or slightly higher GRbeta (5.98 +/- 3.9; p = 0.1) expression than controls, with a GRalpha/GRbeta ratio 15 times smaller than controls. Mononuclear leukocytes of T-cell lineage expressed significantly lower GRalpha (p = 0.04) and higher GRbeta (p < 0.01) than cells of the pre-B immunophenotype, with a 10 times smaller ratio. We conclude that the combination of low GRalpha and normal-to-high GRbeta expression in leukemic lymphoblasts might represent one of the mechanisms responsible for their reduced glucocorticoid sensitivity; this is more pronounced in T-lineage cells. |
| Databáze: | OpenAIRE |
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