Journal
BIOCHEMICAL JOURNAL
Volume 393, Issue -, Pages 21-41Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20051368
Keywords
cAMP; cancer therapy; glueocorticoid; leukaemia; methylxanthine; phosphodiesterase
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Funding
- NCI NIH HHS [R01 CA106705] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA106705] Funding Source: NIH RePORTER
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The cAMP signalling pathway has emerged as a key regulator of haematopoietic cell proliferation, differentiation and apoptosis. In parallel, general understanding of the biology of cyclic nucleotide PDEs (phosphodiesterases) has advanced considerably, revealing the remarkable complexity of this enzyme system that regulates the amplitude, kinetics and location of intracellular cAMP-mediated signalling. The development of therapeutic inhibitors of specific PDE gene families has resulted in a growing appreciation of the potential therapeutic application of PDE inhibitors to the treatment of immune-mediated illnesses and haematopoietic malignancies. This review summarizes the expression and function of PDEs in normal haematopoietic cells and the evidence that family-specific inhibitors will be therapeutically useful in myeloid and lymphoid malignancies.
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