Adenosine deaminase mRNA expression is regulated posttranscriptionally during differentiation of HL-60 cells

The expression of the enzyme adenosine deaminase (ADA) decreases in the course of the differentiation of the human promyelocytic leukemic cell line HL-60, dependent on the pathway chosen. Differentiation to monocytes as induced by the phorbol ester TPA leads to a 50% reduction of enzyme activity. Induction to myeloid cells as induced by DMSO has a slower and less extensive (75% remaining activity) effect. The reduction in ADA enzymatic activity is preceded by a 5-10 fold reduction in ADA-specific mRNA which is also more rapid during TPA-induced differentiation. In contrast, c-myc mRNA expression is both in TPA- and DMSO-induced differentiation reduced to less then 5% of its initial level within 4h. Nuclear run-on analysis revealed that the reduction of c-myc-mRNA expression during both TPA- and DMSO-induced differentiation could be ascribed to the abolition of transcription of the third exon, whereas no change in the transcription of the first exon could be observed. No change could be detected in the rate of transcription of either the 5' and 3' parts of the ADA gene during TPA- and DMSO-induced differentiation, indicating that the expression of the ADA gene in HL-60 is controlled at a posttranscriptional level.