Klinische Wochenschrift

, Volume 63, Issue 15, pp 689–698 | Cite as

Glucocorticoid receptors in human leukemias and related diseases

  • E. B. Thompson
  • J. R. Smith
  • S. Bourgeois
  • J. M. Harmon


The evidence to date is compelling that steroid initiated cell lysis involves participation of the glucocorticoid receptor. Not only do the concentrations and specificity of hormones for cell lysis and receptor occupancy correspond, but also steroid resistant cells selected with or without prior mutagenesis often have altered receptors. The glucocorticoid receptor protein from humans and other species is a ∼ 95,000 d, thiol group-containing monomer, prone to aggregation when “unactivated.” After having bound steroid and been “activated,” the monomeric steroid-receptor complex is altered in charge and shape so that its binding to chromatin and DNA is greatly enhanced. Simple measurement of numbers of receptor sites in cells from patients with various blood dyscrasias has given, in some diseases, good correlations between high numbers of receptor sites and good therapeutic response. These correlations are strongest for childhood acute lymphoblastic leukemia (ALL) and for non Hodgkins' lymphoma. In other diseases, notably acute myelogenous leukemia, such correlations have not been found.

The CEM human ALL line has been used in vitro to study mechanisms of glucocorticoid action and resistance. The requirement for “activated” steroid-receptor complex for cell lysis is shown in these cells by the spontaneous occurrence of steroid resistant, activation-labile receptor mutants. A second category of resistant cells with normal receptors has been defined. Treatment of these “lysis defective” resistant cells with compounds which result in DNA demethylation can render them steroid sensitive. Since DNA demethylation can allow formerly silent genes to become transcribed, it is possible that one or more genes specific for lysis has been “opened” in such cells. Alternatively, DNA demethylation may produce a general biochemical effect on the cell which renders it susceptible to lysis. Mutagenized CEM cells selected for steroid resistance give rise to a third class of mutants, which are deficient in receptor quantity. Each of these classes of steroid resistant cells contains information pertinent to understanding the use of glucocorticoids and the role of glucocorticoid receptors in human leukopathic disease.

Key words

Glucocorticoids Receptors Leukemia Tissue Culture Resistance 



acute lymphoblastic leukemia


acute myelogenous leukemia


chronic lymphoblastic leukemia




reverse phase/high performance liquid chromatography


sodium dodecyl sulfate


sheep red blood cells


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Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • E. B. Thompson
    • 1
  • J. R. Smith
    • 3
  • S. Bourgeois
    • 3
  • J. M. Harmon
    • 4
  1. 1.Laboratory of Biochemistry, National Cancer InstituteNational Institutes of HealthBethesda
  2. 2.Department of Human Biological Chemistry and GeneticsThe University of Texas Medical BranchGalveston
  3. 3.Regulatory Biology LaboratoryThe Salk InstituteSan Diego
  4. 4.Department of PharmacologyUniformed Services University of the Health SciencesBethesda

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