TELOMERASE ACTIVITY IN HUMAN HEMATOPOIETIC PROGENITOR CELLS

Background and Objective. Telomerase is the enzyme that stabilizes and elongates the telomeric ends of chromosomes. It is expressed in germl ine and malignant cells and absent in most human somatic cells. The se lective expression of telomerase has thus been proposed to be a basis for the immortality of germline and malignant cells. Recently, telomer ase activity has been observed in human bone marrow (BM) and periphera l blood (PB) samples. The objective of our study was to further charac terize the telomerase-expressing population in BM and PB. Methods. CD3 4(+) cells were isloated from BM and PB, cultured in vitro, and telome rase activity was assessed by the PCR-based TRAP assay. Results. Telom erase activity in human BM and PB could be almost exclusively assigned to the hematopoietic progenitor cell fraction expressing the CD34 ant igen. We observed telomerase activity in CD34(+) cells from BM and cyt okine-mobilized PB. CD34(+) cells lacking co-expression of CD33 demons trated higher levels of telomerase than myeloid committed CD34(+)/CD33 (+) cells. In vitro culture of CD34(+) cells in the presence of a cock tail of growth factors inducing differentiation resulted in a decrease of telomerase activity. Telomerase activity increased in peripheral b lood during cytokine-induced mobilization of hematopoietic progenitor cells. Interpretation and Conclusions. Our data demonstrate that at le ast a portion of the hematopoietic stem/progenitor cell fraction expre sses telomerase and downregulates its expression through differentiati on. (C) 1997, Ferrata Storti Foundation.