Desmoglein‐2 expression is an independent predictor of poor prognosis patients with multiple myeloma. Issue 6 (24th July 2021)

• Record Type: Journal Article
• Authors: Ebert, Lisa M.; Vandyke, Kate; Johan, M. Zahied; DeNichilo, Mark; Tan, Lih Y.; Myo Min, Kay K.; Weimann, Benjamin M.; Ebert, Brenton W.; Pitson, Stuart M.; Zannettino, Andrew C. W.; Wallington‐Beddoe, Craig T.; Bonder, Claudine S.
• Is Part Of: Molecular oncology. Volume 16:Issue 6(2022)
• Page Start: 1221
• Page End: 1240
• Publication Date: 2021-07-24
• Subjects: adhesion -- bone marrow -- desmoglein‐2 -- multiple myeloma -- plasma cells -- prognostic; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.13055
• Languages: English
• ISSNs: 1574-7891

Abstract

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. Abstract : This study suggests that desmoglein‐2 (DSG2) is a novel cell surface adhesion molecule expressed by neoplastic plasma cells of patients with multiple myeloma. It presents a clear link to poor prognosis of myeloma patients across all cytogenetic subtypes. DSG2 is a readily measurable and clinically useful prognostic biomarker that may prove to be a novel target to combat myeloma progression and improve patient outcomes.