There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Stimulation of the cAMP signaling pathway has been shown to induce apoptosis and augment
the effects of glucocorticoids in inducing apoptosis in leukemic cells. We recently
reported that in primary B cell chronic lymphocytic leukemic (B-CLL) cells, apoptosis
could be induced by stimulating the cAMP signaling pathway with a phosphodiesterase4
(PDE4) inhibitor alone; while in contrast, in the CEM T leukemic cell line, PDE4 inhibitors
alone were ineffective, and concurrent stimulation of adenylyl cyclase was required
to see effects [Tiwari et al. (2005)]. We report here that in the CEM and Jurkat T
leukemic cell lines, the most abundantly expressed PDEs are PDE3B, PDE4A, PDE4D, PDE7A,
and PDE8A. Selective inhibition of PDE3, PDE4 or PDE7 alone produces little effect
on cell viability, but inhibition of all three of these PDEs together dramatically
enhances glucocorticoid-induced apoptosis in CEM cells, and overcomes glucocorticoid
resistance in a glucocorticoid-resistant CEM cell line. These studies indicate that
for some leukemic cell types, a desired therapeutic effect may be achieved by inhibiting
more than one form of PDE.