Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma
Multiple myeloma (MM) is a plasma cell malignancy that is accompanied by hypercalcemia, renal failure, anemia, and lytic bone lesions. Heparanase (HPSE) plays an important role in supporting and promoting myeloma progression, maintenance of plasma cell stemness, and resistance to therapy. Previous s...
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MDPI AG
2023-03-01
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| author | Olga Ostrovsky Katia Beider Hila Magen Merav Leiba Ralph D. Sanderson Israel Vlodavsky Arnon Nagler |
| author_facet | Olga Ostrovsky Katia Beider Hila Magen Merav Leiba Ralph D. Sanderson Israel Vlodavsky Arnon Nagler |
| author_sort | Olga Ostrovsky |
| collection | DOAJ |
| description | Multiple myeloma (MM) is a plasma cell malignancy that is accompanied by hypercalcemia, renal failure, anemia, and lytic bone lesions. Heparanase (HPSE) plays an important role in supporting and promoting myeloma progression, maintenance of plasma cell stemness, and resistance to therapy. Previous studies identified functional single nucleotide polymorphisms (SNPs) located in the HPSE gene. In the present study, 5 functional HPSE SNPs and 11 novel HPSE2 SNPs were examined. A very significant association between two enhancer (rs4693608 and rs4693084), and two insulator (rs4364254 and rs4426765) HPSE SNPs and primary paraskeletal disease (PS) was observed. SNP rs657442, located in intron 9 of the HPSE2 gene, revealed a significant protective association with primary paraskeletal disease and lytic bone lesions. The present study demonstrates a promoting (HPSE gene) and protective (HPSE2 gene) role of gene regulatory elements in the development of paraskeletal disease and bone morbidity. The effect of signal discrepancy between myeloma cells and normal cells of the tumor microenvironment is proposed as a mechanism for the involvement of heparanase in primary PS. We suggest that an increase in heparanase-2 expression can lead to effective suppression of heparanase activity in multiple myeloma accompanied by extramedullary and osteolytic bone disease. |
| first_indexed | 2024-03-11T06:47:48Z |
| format | Article |
| id | doaj.art-96093207e230487dbe545e4390f6fa9f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T06:47:48Z |
| publishDate | 2023-03-01 |
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| record_format | Article |
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| spelling | doaj.art-96093207e230487dbe545e4390f6fa9f2023-11-17T10:13:38ZengMDPI AGCells2073-44092023-03-0112691310.3390/cells12060913Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple MyelomaOlga Ostrovsky0Katia Beider1Hila Magen2Merav Leiba3Ralph D. Sanderson4Israel Vlodavsky5Arnon Nagler6Department of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer 5266202, IsraelDepartment of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer 5266202, IsraelDepartment of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer 5266202, IsraelDepartment of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer 5266202, IsraelDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USATechnion Integrated Cancer Center (TICC), Rappaport Faculty of Medicine, Technion, Haifa 3525433, IsraelDepartment of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer 5266202, IsraelMultiple myeloma (MM) is a plasma cell malignancy that is accompanied by hypercalcemia, renal failure, anemia, and lytic bone lesions. Heparanase (HPSE) plays an important role in supporting and promoting myeloma progression, maintenance of plasma cell stemness, and resistance to therapy. Previous studies identified functional single nucleotide polymorphisms (SNPs) located in the HPSE gene. In the present study, 5 functional HPSE SNPs and 11 novel HPSE2 SNPs were examined. A very significant association between two enhancer (rs4693608 and rs4693084), and two insulator (rs4364254 and rs4426765) HPSE SNPs and primary paraskeletal disease (PS) was observed. SNP rs657442, located in intron 9 of the HPSE2 gene, revealed a significant protective association with primary paraskeletal disease and lytic bone lesions. The present study demonstrates a promoting (HPSE gene) and protective (HPSE2 gene) role of gene regulatory elements in the development of paraskeletal disease and bone morbidity. The effect of signal discrepancy between myeloma cells and normal cells of the tumor microenvironment is proposed as a mechanism for the involvement of heparanase in primary PS. We suggest that an increase in heparanase-2 expression can lead to effective suppression of heparanase activity in multiple myeloma accompanied by extramedullary and osteolytic bone disease.https://www.mdpi.com/2073-4409/12/6/913HPSE geneHPSE2 geneSNPsmultiple myelomaextramedullary disease |
| spellingShingle | Olga Ostrovsky Katia Beider Hila Magen Merav Leiba Ralph D. Sanderson Israel Vlodavsky Arnon Nagler Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma Cells HPSE gene HPSE2 gene SNPs multiple myeloma extramedullary disease |
| title | Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma |
| title_full | Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma |
| title_fullStr | Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma |
| title_full_unstemmed | Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma |
| title_short | Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma |
| title_sort | effect of hpse and hpse2 snps on the risk of developing primary paraskeletal multiple myeloma |
| topic | HPSE gene HPSE2 gene SNPs multiple myeloma extramedullary disease |
| url | https://www.mdpi.com/2073-4409/12/6/913 |
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