{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:37:39Z","timestamp":1760236659780,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["grant 1021\/19"],"award-info":[{"award-number":["grant 1021\/19"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001698","name":"Israel Cancer Research Fund","doi-asserted-by":"publisher","award":["no"],"award-info":[{"award-number":["no"]}],"id":[{"id":"10.13039\/100001698","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the DKFZ-MOST cancer research program","award":["no"],"award-info":[{"award-number":["no"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Heparanase is an endo-\u03b2-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.<\/jats:p>","DOI":"10.3390\/cells10123489","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T08:17:58Z","timestamp":1639124278000},"page":"3489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["CMV Seropositive Status Increases Heparanase SNPs Regulatory Activity, Risk of Acute GVHD and Yield of CD34+ Cell Mobilization"],"prefix":"10.3390","volume":"10","author":[{"given":"Olga","family":"Ostrovsky","sequence":"first","affiliation":[{"name":"Chaim Sheba Medical Center, Department of Hematology and Bone Marrow Transplantation, Tel-Hashomer, Ramat Gan 5266202, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia","family":"Beider","sequence":"additional","affiliation":[{"name":"Chaim Sheba Medical Center, Department of Hematology and Bone Marrow Transplantation, Tel-Hashomer, Ramat Gan 5266202, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Morgulis","sequence":"additional","affiliation":[{"name":"Chaim Sheba Medical Center, Department of Hematology and Bone Marrow Transplantation, Tel-Hashomer, Ramat Gan 5266202, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nira","family":"Bloom","sequence":"additional","affiliation":[{"name":"Chaim Sheba Medical Center, Department of Hematology and Bone Marrow Transplantation, Tel-Hashomer, Ramat Gan 5266202, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angel","family":"Cid-Arregui","sequence":"additional","affiliation":[{"name":"German Cancer Research Center, D-69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avichai","family":"Shimoni","sequence":"additional","affiliation":[{"name":"Chaim Sheba Medical Center, Department of Hematology and Bone Marrow Transplantation, Tel-Hashomer, Ramat Gan 5266202, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Israel","family":"Vlodavsky","sequence":"additional","affiliation":[{"name":"Technion Integrated Cancer Center, Rappaport Faculty of Medicine, Technion, Haifa 3525433, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0763-1265","authenticated-orcid":false,"given":"Arnon","family":"Nagler","sequence":"additional","affiliation":[{"name":"Chaim Sheba Medical Center, Department of Hematology and Bone Marrow Transplantation, Tel-Hashomer, Ramat Gan 5266202, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"ref_1","first-page":"3","article-title":"Forty Years of Basic and Translational Heparanase Research","volume":"1221","author":"Vlodavsky","year":"2020","journal-title":"Recent Adv. 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