Low glucocorticoid receptor α/β ratio in T-cell lymphoblastic leukemia

C. A. Longui, A. Vottero, P. C. Adamson, D. E. Cole, Tomoshige Kino, O. Monte, G. P. Chrousos

Research output: Contribution to journalArticle

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Abstract

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 α 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 (GRβ), which exerts a dominant negative effect on GRα-mediated transcriptional activity, has been proposed as a possible mediator of glucocorticoid resistance. In this study, we determined the amount of GRα and GRβ 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 GRα (ALL=0.54 ± 1.1; controls= 3.1 ± 0.9; p < 0.01) than controls, but the same amount of GRβ (ALL= 3.62 ± 3.3; controls = 3.6 ± 3.4). ALL patients with T-cell disease had a much lower GRα (0.09 ± 0.1; p < 0.01) but a similar or slightly higher GRβ (5.98 ± 3.9; p = 0.1) expression than controls, with a GRα/GRβ ratio 15 times smaller than controls. Mononuclear leukocytes of T-cell lineage expressed significantly lower GRα (p = 0.04) and higher GRβ (p < 0.01) than cells of the pre-B immunophenotype, with a 10 times smaller ratio. We conclude that the combination of low GRα and normal-to-high GRβ expression in leukemic lymphoblasts might represent one of the mechanisms responsible for their reduced glucocorticoid sensitivity; this is more pronounced in T-lineage cells.

Original languageEnglish
Pages (from-to)401-406
Number of pages6
JournalHormone and Metabolic Research
Volume32
Issue number10
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

T-Cell Leukemia
T-cells
Glucocorticoid Receptors
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Glucocorticoids
Cell Lineage
Protein Isoforms
T-Lymphocytes
Mononuclear Leukocytes
B-Lymphoid Precursor Cells
Cell proliferation
Cell death

Keywords

  • Acute Leukemia
  • Glucocorticoid Receptor
  • Glucocorticoid Resistance
  • Glucocorticoid Sensitivity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Longui, C. A., Vottero, A., Adamson, P. C., Cole, D. E., Kino, T., Monte, O., & Chrousos, G. P. (2000). Low glucocorticoid receptor α/β ratio in T-cell lymphoblastic leukemia. Hormone and Metabolic Research, 32(10), 401-406.

Low glucocorticoid receptor α/β ratio in T-cell lymphoblastic leukemia. / Longui, C. A.; Vottero, A.; Adamson, P. C.; Cole, D. E.; Kino, Tomoshige; Monte, O.; Chrousos, G. P.

In: Hormone and Metabolic Research, Vol. 32, No. 10, 2000, p. 401-406.

Research output: Contribution to journalArticle

Longui, CA, Vottero, A, Adamson, PC, Cole, DE, Kino, T, Monte, O & Chrousos, GP 2000, 'Low glucocorticoid receptor α/β ratio in T-cell lymphoblastic leukemia', Hormone and Metabolic Research, vol. 32, no. 10, pp. 401-406.
Longui CA, Vottero A, Adamson PC, Cole DE, Kino T, Monte O et al. Low glucocorticoid receptor α/β ratio in T-cell lymphoblastic leukemia. Hormone and Metabolic Research. 2000;32(10):401-406.
Longui, C. A. ; Vottero, A. ; Adamson, P. C. ; Cole, D. E. ; Kino, Tomoshige ; Monte, O. ; Chrousos, G. P. / Low glucocorticoid receptor α/β ratio in T-cell lymphoblastic leukemia. In: Hormone and Metabolic Research. 2000 ; Vol. 32, No. 10. pp. 401-406.
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