Glucocorticoid receptors in acute leukemia

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Glucocorticoid receptors (GR) play a crucial role in cellular response to glucocorticoids.
• Predicting clinical responsiveness to polychemotherapy in acute leukemias remains a significant challenge.

Purpose of the Study:

• To evaluate the utility of determining glucocorticoid receptor (GR) levels for predicting clinical response to polychemotherapy in acute leukemias.
• To compare GR levels in leukemic cells with those in normal lymphocytes.

Main Methods:

• Measurement of GR in leukemic cells from 20 acute leukemia patients and lymphocytes from 20 healthy volunteers.
• Utilized a whole-cell binding assay with [3H]-dexamethasone to quantify GR.
• Analyzed the correlation between GR levels and clinical responsiveness to polychemotherapy.

Main Results:

• Acute lymphoblastic leukemia (ALL) cells showed significantly higher GR concentrations (5300-17,000 sites/cell) compared to normal lymphocytes (4583 +/- 1384 sites/cell).
• Absence of GR in ALL patients correlated with a poor response to polychemotherapy, including glucocorticoids.
• High GR levels in ALL were associated with complete remission (P < 0.005).
• Acute non-lymphoblastic leukemia (ANLL) patients also had significantly higher GR concentrations than normal lymphocytes (P < 0.05), but no correlation with clinical response was observed.

Conclusions:

• GR determination is a valuable tool for predicting polychemotherapy response in acute lymphoblastic leukemia (ALL).
• High GR levels predict a favorable response and complete remission in ALL patients.
• GR levels do not appear to predict clinical responsiveness in acute non-lymphoblastic leukemia (ANLL).