Potentiation between intracellular cyclic-AMP-elevating agents and inducers of leukemic cell differentiation.
Acute leukemia is the result of a defect in the process of normal cellular differentiation. Human leukemia cell lines (HL60, RDFD-2) have been established which can be induced to differentiate into phenotypically mature cells by a variety of agents. Recent evidence suggests that cyclic adenosine 3'-5'-monophosphate (cAMP) and the cAMP dependent protein kinase (cAMP-dPK) may be intimately involved in myeloid differentiation. The addition of low levels of a wide variety of inducers of a diverse chemical nature, dimethylformamide (DMF), retinoic acid (RA), actinomycin D (ACT-D) or hypoxanthine (HPX) prior to the addition of 8-bromo-cyclic adenosine 3'-5' monophosphate (8-Br-cAMP), cholera toxin (CT) or the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) results in marked potentiation of differentiation of both HL60 and RDFD cells as manifested by the acquisition of the antigen OKM-1, the ability to reduce nitroblue tetrazolium or expression of the chemotactic receptor. Potentiation of differentiation is also observed when 8-Br-cAMP, CT or IBMX is added prior to the addition of either RA, DMF, ACT-D or HPX. These results suggest a role for cAMP in myeloid differentiation.
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J
Fontana
M
M
Munoz
J
J
Durham
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D004126:Dimethylformamide / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
D007042:Hypoxanthines; D003609:Dactinomycin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019271:Hypoxanthine; D014212:Tretinoin; D004126:Dimethylformamide; D002772:Cholera Toxin; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine