Induction of telomerase activity during development of human mast cells from peripheral blood CD34(+) cells: Comparisons with tumor mast-cell lines

To further characterize the development of mast cells from human hemopoieti c pluripotent cells we have investigated the expression of telomerase activ ity in cultured human peripheral blood CD34(+) cells, and CD34(+)/CD117(+)/ CD13(+) progenitor mast cells selected therefrom, with the idea that induct ion of telomerase is associated with clonal expansion of CD34(+)/CD117(+)/C D13(+) cells. A rapid increase in telomerase activity preceded proliferatio n of both populations of cells in the presence of stern Cell factor and eit her IL-3 or IL-6. The induction was transient, and telomerase activity decl ined to basal levels well before the appearance of mature mast cells. Studi es with pharmacologic inhibitors suggested that this induction was initiall y dependent on the p38 mitogen-activated protein kinase and phosphatidylino sitol 3 ' -kinase, but once cell replication was underway telomerase activi ty, but not cell replication, became resistant to the effects of inhibitors . Tumor mast cell lines, in contrast, expressed persistently high telomeras e activity throughout the cell cycle, and this expression was unaffected by inhibitors of all known signaling pathways in mast cells even when cell pr oliferation was blocked for extended periods. These results suggest that th e transient induction of telomerase activity in human progenitor mast cells was initially dependent on growth factor-mediated signals, whereas mainten ance of high activity in tumor mast cell lines was not dependent on intrace llular signals or cell replication.