PRIMING OF HUMAN MYELOID LEUKEMIC-CELL LINES HL-60 AND U-937 WITH RETINOIC ACID FOR DIFFERENTIATION EFFECTS OF CYCLIC ADENOSINE 3'-5'-MONOPHOSPHATE-INDUCING AGENTS AND A LYMPHOCYTE-T DERIVED DIFFERENTIATION FACTOR

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (10) , 3928-3933
Abstract
The human cell lines HL-60 (acute promyelocytic leukemia) and U-937 (histiocytic monoblast-like lymphoma) differentiate to functionally mature cells by incubation with retinoic acid (RA). This differentiation is potentiated by agents known to increase intracellular cAMP levels. These cells can be primed for differentiation by treatment for approximately 1 day with RA followed by exposure to cAMP-inducing agent. The reverse sequence was ineffective. HL-60 could be primed by incubation for < 20 h with 10 nM RA to respond by differentiation to the addition of 10 nM prostaglandin E2 or 1 nM cholera toxin, whereas 10 nM RA alone was almost inactive. RA-primed HL-60 also responded with differentiation to a concentration of T-lymphocyte-derived differentiation-inducing factor which alone was inactive. U-937 primed by incubation for 24 h with 100 nM RA responded to cAMP-inducing agents and differentiation-inducing factor, which alone were inactive on this cell line. Priming of these cell lines does not depend on the normal rate of protein synthesis, as it occurs even better in the presence of a concentration of cycloheximide that inhibits growth completely, suggesting that a decrease in synthesis of some protein(s) favors RA-induced differentiation. Cycloheximide alone produced some priming of HL-60 but not of U-937. HL-60 but not U-937 primed with RA responded to ATP and other nucleoside triphosphates, consistent with the notion that modulation of the RA effect may be mediated through protein kinase activity at the plasma membrane. Myeloid cell lines, like HL-60 and U-937, blocked at a late stage of maturation can be primed by RA to respond to cAMP-inducing agents and differentiation-inducing factor may improve understanding of the arrest in maturation typical of some forms of leukemia.

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