Adenosine 3′:5′ cyclic monophosphate and myeloid leukemic cell proliferation in vitro

Abstract

In order to elucidate the possible role of adenosine 3′:5′ cyclic monophosphate (cAMP) in the modulation of proliferation of human leukemic myeloblasts, we have determined cAMP levels of samples from patients with leukemia before and after in vitro suspension culture, in the presence and absence of leucocyte conditioned medium (LCM). cAMP levels correlated with the magnitude of increase of cell numbers after culture with LCM (rank-order correlation coefficient ( r s ) = 0.57, P < 0.05) and with tritiated thymidine ( 3H TdR) incorporation during culture ( r s ) = 0.68, P < 0.01). Additions of the phosphodiesterase resistant analogue 8-bromo cAMP to cultures caused modest increases of 3H TdR incorporation of 8 of 9 acute myeloid leukemia samples after 72h with LCM. Stimulation was optimal at 10 −7 M but in the absence of LCM occurred less often and required higher concentrations (10 −5 M). Inhibition was noted at concentrations of 10 −4 M and greater. Cells cultured in the presence of LCM had lower levels of cAMP ( P < 0.01) particularly at points with maximal stimulation of 3H TdR incorporation ( P < 0.01). These differences between paired points (with and without LCM) were small and no immediate effect of LCM upon cAMP levels, after 1 and 2-h incubations, was noted. These data suggest that cAMP promotes initiation of leukemic cell proliferation in vitro.