TY  - JOUR
AU  - Ostrovsky, Olga
AU  - Beider, Katia
AU  - Morgulis, Yan
AU  - Bloom, Nira
AU  - Cid-Arregui, Angel
AU  - Shimoni, Avichai
AU  - Vlodavsky, Israel
AU  - Nagler, Arnon
TI  - CMV Seropositive Status Increases Heparanase SNPs Regulatory Activity, Risk of Acute GVHD and Yield of CD34+ Cell Mobilization.
JO  - Cells
VL  - 10
IS  - 12
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - DKFZ-2021-03252
SP  - 3489
PY  - 2021
AB  - Heparanase is an endo-β-glucuronidase that is best known for its pro-cancerous effects but is also implicated in the pathogenesis of various viruses. Activation of heparanase is a common strategy to increase viral spread and trigger the subsequent inflammatory cascade. Using a Single Nucleotide Polymorphisms (SNP)-associated approach we identified enhancer and insulator regions that regulate HPSE expression. Although a role for heparanase in viral infection has been noticed, the impact of HPSE functional SNPs has not been determined. We investigated the effect of cytomegalovirus (CMV) serostatus on the involvement of HPSE enhancer and insulator functional SNPs in the risk of acute graft versus host disease (GVHD) and granulocyte-colony stimulating factor related CD34+ mobilization. A significant correlation between the C alleles of insulator rs4364254 and rs4426765 and CMV seropositivity was found in healthy donors and patients with hematological malignancies. The risk of developing acute GVHD after hematopoietic stem cell transplantation was identified only in CMV-seropositive patients. A significant correlation between the enhancer rs4693608 and insulator rs28649799 and CD34+ cell mobilization was demonstrated in the CMV-seropositive donors. It is thus conceivable that latent CMV infection modulates heparanase regulatory regions and enhances the effect of functional SNPs on heparanase function in normal and pathological processes.
KW  - CMV (Other)
KW  - G-CSF-mobilization (Other)
KW  - HPSE gene (Other)
KW  - SNPs (Other)
KW  - acute GVHD (Other)
KW  - allogeneic HSCT (Other)
KW  - enhancer (Other)
KW  - insulator (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34943994
C2  - pmc:PMC8700738
DO  - DOI:10.3390/cells10123489
UR  - https://inrepo02.dkfz.de/record/178305
ER  -