TY - JOUR
T1 - Ganciclovir Inhibits Lymphocyte Proliferation by Impairing DNA Synthesis
AU - Battiwalla, Minoo
AU - Wu, Yiyuan
AU - Bajwa, Rajinder P.S.
AU - Radovic, Marija
AU - Almyroudis, Nikolaos G.
AU - Segal, Brahm H.
AU - Wallace, Paul K.
AU - Nakamura, Ryotaro
AU - Padmanabhan, Swaminathan
AU - Hahn, Theresa
AU - McCarthy, Philip L.
N1 - Funding Information:
This work was independent of commercial support. Flow cytometry was performed at Roswell Park Cancer Institute’s Flow Cytometry Laboratory, which was established in part by equipment grants from the NIH Shared Instrument Program, and receives support from the Core Grant (5 P30 CA016056-29) from the National Cancer Institute to the Roswell Park Cancer Institute. We thank Francisco Hernandez, MD, for the gift of the Raji cell line and the HD10 antibody, and Earl Timm, PhD, for his expertise with flow cytometry.
PY - 2007/7
Y1 - 2007/7
N2 - Cytomegalovirus (CMV) disease-related mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients has dramatically declined because of ganciclovir prophylaxis and preemptive therapeutic strategies. However, ganciclovir has not improved overall survival in randomized studies despite effectively preventing overt CMV disease. Moreover, recurrent posttransplant CMV antigenemia, associated with prolonged ganciclovir exposure, is a predictor of increased relapse of malignancy. We examined the hypothesis that ganciclovir itself may have a negative impact on immune reconstitution by testing the effect of ganciclovir on normal human lymphocytes in vitro. T-lymphocyte activation and proliferation, as measured by PHA-induced 3H-thymidine uptake, was greatly reduced at therapeutic concentrations of ganciclovir (10 μg/mL) but not for foscarnet (300 μM/L). Moreover, ganciclovir impaired bromodeoxyuridine incorporation in proliferating lymphocytes, but did not impair lymphocyte survival or induce lymphocyte apoptosis. Collectively, these results show that ganciclovir suppresses T-lymphocyte proliferation in vitro by inhibiting DNA synthesis; with implications for T-lymphocyte function following allogeneic BMT.
AB - Cytomegalovirus (CMV) disease-related mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients has dramatically declined because of ganciclovir prophylaxis and preemptive therapeutic strategies. However, ganciclovir has not improved overall survival in randomized studies despite effectively preventing overt CMV disease. Moreover, recurrent posttransplant CMV antigenemia, associated with prolonged ganciclovir exposure, is a predictor of increased relapse of malignancy. We examined the hypothesis that ganciclovir itself may have a negative impact on immune reconstitution by testing the effect of ganciclovir on normal human lymphocytes in vitro. T-lymphocyte activation and proliferation, as measured by PHA-induced 3H-thymidine uptake, was greatly reduced at therapeutic concentrations of ganciclovir (10 μg/mL) but not for foscarnet (300 μM/L). Moreover, ganciclovir impaired bromodeoxyuridine incorporation in proliferating lymphocytes, but did not impair lymphocyte survival or induce lymphocyte apoptosis. Collectively, these results show that ganciclovir suppresses T-lymphocyte proliferation in vitro by inhibiting DNA synthesis; with implications for T-lymphocyte function following allogeneic BMT.
KW - CMV
KW - DNA polymerase
KW - Ganciclovir
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U2 - 10.1016/j.bbmt.2007.03.009
DO - 10.1016/j.bbmt.2007.03.009
M3 - Article
C2 - 17580254
AN - SCOPUS:34250208050
VL - 13
SP - 765
EP - 770
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 7
ER -