Molecular determinants of glucocorticoid sensitivity and resistance in acute lymphoblastic leukemia

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138 Citaten (Scopus)

Samenvatting

Glucocorticoids (GC) are probably the most important drugs in the treatment of ALL. Despite the extensive use of GC for many years, little is known about the molecular mechanisms of sensitivity and resistance. This review summarizes the knowledge on GC cytotoxicity in leukemia. The relevance of polymorphisms, splice variants and the number and regulation of the GC receptor are discussed. The role of multidrug resistance proteins, glutathione and glutathione S-transferase is evaluated, as well as the influence of the different heat-shock chaperone (hsp 90 and 70) and co-chaperone proteins (BAG-1 and others) which form a complex together with the GC receptor. Finally, the transactivation and transrepression (via NF-kappa B and AP-1 binding) of a wide range of genes (like c-myc) which initiates the final apoptosis pathway are discussed and suggestions for future directions of research in ALL patients are given.

Originele taal-2Engels
Pagina's (van-tot)17-25
Aantal pagina's9
TijdschriftLeukemia
Volume17
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - jan. 2003
Extern gepubliceerdJa

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