Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma

Olga Ostrovsky, Katia Beider, Hila Magen, Merav Leiba, Ralph D. Sanderson, Israel Vlodavsky, Arnon Nagler

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number913
JournalCells
Volume12
Issue number6
DOIs
StatePublished - 1 Mar 2023
Externally publishedYes

Keywords

  • HPSE gene
  • HPSE2 gene
  • SNPs
  • extramedullary disease
  • multiple myeloma

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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