PGE(2) receptor subtype functionality on immature forms of human leukemic blasts

Abstract

The ability of prostaglandin E2 (PGE2) to regulate the immune system is well documented. PGE2 effects are mediated through interactions with four distinct membrane EP receptors (EP(1-4)). We investigated, for the first time, the functionality of EP receptors on immature forms of blast cells of acute myeloid leukemic (AML) and acute lymphoid leukemic (ALL) patients. RT-PCR experiments documented the presence of the four EP receptor subtype transcripts in leukemic blasts of AML M0, AML M1, AML M2 and ALL patients. Western blot analysis only documented the presence of the EP2 receptor. Functional assays (cAMP production, calcium flux) confirmed Western blot results, i.e., the presence of functional EP2 receptors. Results of the present study suggest that the mechanism used by PGE2 to influence blast physiology is mediated through the EP2 receptor subtype, and subsequently through a cAMP-elevating effect. Results obtained with M0-2 subtypes have to be necessarily extended to more differentiated phenotype.