Telomerase activity in human hematopoietic progenitor cells.
OBJECTIVE
Telomerase is the enzyme that stabilizes and elongates the telomeric ends of chromosomes. It is expressed in germline and malignant cells and absent in most human somatic cells. The selective expression of telomerase has thus been proposed to be a basis for the immortality of germline and malignant cells. Recently, telomerase activity has been observed in human bone marrow (BM) and peripheral blood (PB) samples. The objective of our study was to further characterize the telomerase-expressing population in BM and PB.


METHODS
CD34+ cells were isolated from BM and PB, cultured in vitro, and telomerase activity was assessed by the PCR-based TRAP assay.


RESULTS
Telomerase activity in human BM and PB could be almost exclusively assigned to the hematopoietic progenitor cell fraction expressing the CD34 antigen. We observed telomerase activity in CD34+ cells from BM and cytokine-mobilized PB. CD34+ cells lacking co-expression of CD33 demonstrated higher levels of telomerase than myeloid committed CD34+/CD33+ cells. In vitro culture of CD34+ cells in the presence of a cocktail of growth factors inducing differentiation resulted in a decrease of telomerase activity. Telomerase activity increased in peripheral blood during cytokine-induced mobilization of hematopoietic progenitor cells.


CONCLUSIONS
Our data demonstrate that at least a portion of the hematopoietic stem/progenitor cell fraction expresses telomerase and downregulates its expression through differentiation.
Hohaus
S
S
Department of Medical Genetics, Università Cattolica S. Cuore, Rome, Italy. stefan_hohaus@krzmail.krz.uni-heidelberg.de
Voso
M T
MT
Orta-La Barbera
E
E
Cavallo
S
S
Bellacosa
A
A
Rutella
S
S
Rumi
C
C
Genuardi
M
M
Neri
G
G
Leone
G
G
D018952:Antigens, CD34 / Q000032:analysis; D001773:Blood Cells / Q000201:enzymology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004790:Enzyme Induction; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008223:Lymphoma / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000201:enzymology; D016133:Polymerase Chain Reaction; D019098:Telomerase / Q000032:analysis*; D014407:Tumor Cells, Cultured
D018952:Antigens, CD34; D016298:Hematopoietic Cell Growth Factors; D019098:Telomerase