Desmoglein-2 expression is an independent predictor of poor prognosis patients with multiple myeloma

Lisa M. Ebert, Kate Vandyke, Mohammad Z Johan, Mark DeNichilo, Tan Lih, Kay K Myo Min, Benjamin Weimann, Brenton W. Ebert, Stuart M. Pitson, Andrew C.W. Zannettino, Craig Wallington-Beddoe, Claudine S. Bonder

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Abstract

Multiple myeloma (MM) is the second most common haematological malignancy and is an incurable disease of neoplastic plasma cells (PC). Newly diagnosed MM patients currently undergo lengthy genetic testing to match chromosomal mutations with the most potent drug/s to decelerate disease progression. With only 17% of MM patients surviving 10-years postdiagnosis, faster detection and earlier intervention would unequivocally improve outcomes. Here, we show that the cell surface protein desmoglein-2 (DSG2) is overexpressed in ˜ 20% of bone marrow biopsies from newly diagnosed MM patients. Importantly, DSG2 expression was strongly predictive of poor clinical outcome, with patients expressing DSG2 above the 70 th percentile exhibiting an almost 3-fold increased risk of death. As a prognostic factor, DSG2 is independent of genetic subtype as well as the routinely measured biomarkers of MM activity (e.g. paraprotein). Functional studies revealed a nonredundant role for DSG2 in adhesion of MM PC to endothelial cells. Together, our studies suggest DSG2 to be a potential cell surface biomarker that can be readily detected by flow cytometry to rapidly predict disease trajectory at the time of diagnosis.

Original languageEnglish
Number of pages41
JournalMolecular Oncology
DOIs
Publication statusE-pub ahead of print - 10 Jul 2021

Keywords

  • Desmoglein-2
  • Multiple Myeloma
  • Predictors
  • prognostic
  • multiple myeloma
  • desmoglein-2
  • adhesion
  • plasma cells
  • bone marrow

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