Glucocorticoid-binding proteins in human acute lymphoblastic leukemic blast cells

Area of Science:

• Endocrinology
• Molecular Biology
• Oncology

Background:

• Steroid hormone action initiates with steroid binding to cytoplasmic steroid-binding proteins (SBP).
• Glucocorticoids are vital in treating human lymphoblastic leukemia.

Purpose of the Study:

• To detect, quantify, and characterize SBP in glucocorticoid-sensitive human lymphoblastic leukemic blasts.
• To investigate the correlation between SBP activity and glucocorticoid sensitivity in leukemia.

Main Methods:

• Competitive binding assays were used to detect and quantify SBP in leukemic cell cytosol.
• In vitro inhibition of [(3)H]thymidine uptake was measured to assess glucocorticoid potency.
• SBP activity was assessed in both glucocorticoid-sensitive and -resistant leukemic cells from patients.

Main Results:

• A specific SBP was identified and characterized in glucocorticoid-sensitive human lymphoblastic leukemic blasts.
• Steroid affinity for SBP correlated directly with their known cytotoxic potency.
• SBP activity was significantly reduced or absent in glucocorticoid-resistant cells and in patients who lost responsiveness to glucocorticoids.
• Leukemic cells lacking SBP activity showed no inhibition of [(3)H]thymidine uptake by steroids.

Conclusions:

• This study provides the first evidence of glucocorticoid receptors (via SBP) in human tissue.
• SBP plays an essential physiological role in mediating glucocorticoid action in leukemia.
• SBP levels can serve as a predictive biomarker for glucocorticoid responsiveness in lymphoblastic leukemia treatment.