Resistance to glucocorticoid-induced apoptosis in lymphoblastic leukemia

Journal of Endocrinology - Tập 178 Số 1 - Trang 19-27 - 2003
Reinhard Kofler1,2, Stefan Schmidt2, Anita Kofler3, Michael J. Ausserlechner1,2
1Institute of Pathophysiology, Division of Molecular Pathophysiology, University of Innsbruck Medical School; Fritz-Pregl-Str. 3; A-6020 Innsbruck, Austria
2Tyrolean Cancer Research Institute at the University of Innsbruck; Innrain 66; A-6020 Innsbruck, Austria
3Tyrolean Cancer Research Institute, Innrain 66, A-6020 Innsbruck, Austria

Tóm tắt

Glucocorticoid (GC) resistance is a phenomenon of major significance in a number of clinical situations, including the therapy of lymphoid malignancies. Resistance may concern all, or just selected, GC effects, it may be absolute or just reflect a state of reduced sensitivity and, clinically relevant, be reversible or irreversible. Numerous molecular mechanisms can be envisaged acting either 'upstream' in the GC-triggered signaling pathway, i.e. at the level of the GC receptor (GR), or 'downstream' at the level of the GC-regulated genes responsible for individual GC effects. In lymphoid malignancies, GCs have anti-leukemic effects through the induction of apoptosis and/or cell cycle arrest. In this condition evidence for only a small number of mechanisms for GC resistance has been provided, mostly at the level of the GR. Herein, we review reports and hypotheses regarding 'upstream' and 'downstream' mechanisms for GC resistance in lymphoblastic leukemia and present an in vitro GC resistance model that might allow identification of resistance mechanisms.

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Journal of Endocrinology

Tập 178 Số 1

19-27

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