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Glucocorticoid induced apoptosis in leukemia
L A Smets1, G Salomons, J van den Berg
1Department of Experimental Therapy, Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Amsterdam.
Abstract:
Lymphoid and leukemic cells are uniquely sensitive to the lytic actions of glucocorticoid hormones which activate a programmed cell death in these cells. The response to glucocorticoids is sensitive to modulations at each step of hormone action: cellular uptake, binding and activation of cytosolic receptors, nuclear translocation and transcriptional activity of the activated receptor and the expression levels of pro- and anti-apoptotic genes. This review, based mainly on our studies with leukemic cells in tissue culture and on clinical observations in childhood acute lymphoblastic leukemia, summarizes the potential impact of these checkpoints in the treatment of this disease. In addition, we will discuss interventions that may reverse resistance or promote sensitivity to apoptosis of leukemic cells by glucocorticoid hormones.
Insights
Glucocorticoids induce programmed cell death in lymphoid and leukemic cells. Understanding these hormone actions can help reverse resistance and improve leukemia treatment.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- Lymphoid and leukemic cells exhibit unique sensitivity to glucocorticoids, which trigger apoptosis.
- Glucocorticoid hormone action involves multiple steps, including cellular uptake, receptor activation, nuclear translocation, and gene expression.
- Resistance to glucocorticoid-induced apoptosis is a significant challenge in treating acute lymphoblastic leukemia.
Purpose of the Study:
- To review the mechanisms of glucocorticoid action and apoptosis in leukemic cells.
- To summarize the impact of various checkpoints in glucocorticoid hormone action on treatment efficacy.
- To discuss potential interventions to overcome resistance and enhance glucocorticoid sensitivity in leukemia.
Main Methods:
- Review of studies on leukemic cells in tissue culture.
- Analysis of clinical observations in childhood acute lymphoblastic leukemia.
- Examination of molecular pathways regulating apoptosis.
Main Results:
- Glucocorticoid response is modulated at multiple levels, affecting hormone action and apoptosis.
- Checkpoints in glucocorticoid signaling can influence treatment outcomes in leukemia.
- Interventions targeting these checkpoints may reverse resistance to glucocorticoid therapy.
Conclusions:
- Understanding the intricacies of glucocorticoid action is crucial for optimizing leukemia treatment.
- Targeting specific steps in glucocorticoid signaling pathways holds promise for overcoming therapeutic resistance.
- Further research into reversing resistance mechanisms can improve patient outcomes in acute lymphoblastic leukemia.