Low glucocorticoid receptor alpha/beta ratio in T-cell lymphoblastic leukemia

Low glucocorticoid receptor alpha/beta ratio in T-cell lymphoblastic leukemia

Autor Longui, C. A. Google Scholar
Vottero, A. Google Scholar
Adamson, P. C. Google Scholar
Cole, D. E. Google Scholar
Kino, T. Google Scholar
Monte, O. Google Scholar
Chrousos, G. P. Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Santa Casa São Paulo
NICHD
NCI
Resumo 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 cr 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 CR isoform (GR beta), which exerts a dominant negative effect on GR alpha -mediated transcriptional activity, has been proposed as a possible mediator of glucocorticoid resistance. in this study, we determined the amount of GR alpha and GR beta 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 GR alpha (ALL = 0.54 +/- 1.1; controls = 3.1 +/- 0.9; p < 0.01) than controls, but the same amount of GRP (ALL = 3.62 +/- 3.3: controls = 3.6 +/- 3.4). ALL patients with T-cell disease had a much lower GR<alpha> (0.09 +/- 0.1;p < 0.01) but a similar or slightly higher GR<beta> (5.98 +/- 3.9: p = 0.1) expression than controls, with a GR alpha /GR beta ratio 15 times smaller than controls. Mononuclear leukocytes of T-cell lineage expressed significantly lower GR alpha (p = 0.04) and higher CR beta (p < 0.01) than cells of the pre-B immunophenotype, with a 10 times smaller ratio. We conclude that: the combination of low GR<alpha> and normal-to-high GR beta expression in leukemic lymphoblasts might represent one of the mechanisms responsible for their reduced glucocorticoid sensitivity; this is more pronounced in T-lineage cells.
Palavra-chave glucocorticoid receptor
acute leukemia
glucocorticoid sensitivity
glucocorticoid resistance
Idioma Inglês
Data de publicação 2000-10-01
Publicado em Hormone and Metabolic Research. Stuttgart: Georg Thieme Verlag Kg, v. 32, n. 10, p. 401-406, 2000.
ISSN 0018-5043 (Sherpa/Romeo, fator de impacto)
Publicador Georg Thieme Verlag Kg
Extensão 401-406
Fonte http://dx.doi.org/10.1055/s-2007-978661
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000090144600004
Endereço permanente http://repositorio.unifesp.br/handle/11600/26394

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