Human T cell leukemia virus type II increases telomerase activity in uninfected CD34+ hematopoietic progenitor cells.
The aging process of long-term self-renewing hematopoietic stem/progenitor cells is not yet completely understood and recent studies on antiapoptotic cell pathways have demonstrated a close linkage between telomerase activation and Bcl-2 deregulation in human cancer cells. The present work shows that human T cell leukemia virus type II (HTLV-II) Mo virions that have originated from the T cell line (C344), but not from the B cell line (BJAB), are critically involved in mediating survival and growth effects on hematopoietic precursors (represented by both the TF-1 CD34+ cell line and by peripheral blood-derived CD34+ cells) through the maintenance or enhancement of telomerase activity and the induction of bcl-2 expression. In addition, using an interleukin-3-dependent TF-1 cell line, it was demonstrated that IL-3 deprivation was sufficient to influence the levels of telomerase activity and Bcl-2 expression in CD34+ cells. Taken together, these findings suggest that, in appropriate conditions, extended hematopoietic progenitor cell survival and proliferation following HTLV-II exposure depends on a synergistic interaction between up-regulation of Bcl-2 and activation of telomerase activity.
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Department of Clinical and Experimental Medicine, University of Bologna, Italy.
Monari
P
P
Gibellini
D
D
Ciancianaini
P
P
Dall'Aglio
P P
PP
Vignoli
M
M
Furlini
G
G
Ramazzotti
E
E
Bertazzoni
U
U
Casoli
C
C
D018952:Antigens, CD34 / Q000032:analysis*; D001402:B-Lymphocytes / Q000201:enzymology / Q000821:virology; D005786:Gene Expression Regulation / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000201:enzymology* / Q000276:immunology* / Q000821:virology; D015367:Human T-lymphotropic virus 2 / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000821:virology; D019098:Telomerase / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000821:virology; D014771:Virion / Q000502:physiology
D018952:Antigens, CD34; D007377:Interleukin-3; D019253:Proto-Oncogene Proteins c-bcl-2; D019098:Telomerase