Desmoglein-2 expression is an independent predictor of poor prognosis patients with multiple myeloma
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(Published version)
Date
2022
Authors
Ebert, L.M.
Vandyke, K.
Johan, M.Z.
DeNichilo, M.
Tan, L.Y.
Myo Min, K.K.
Weimann, B.M.
Ebert, B.W.
Pitson, S.M.
Zannettino, A.C.W.
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Journal article
Citation
Molecular Oncology, 2022; 16(6):1221-1240
Statement of Responsibility
Lisa M. Ebert, Kate Vandyke, M. Zahied Johan, Mark DeNichilo, Lih Y. Tan
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Abstract
Multiple myeloma (MM) is the second most common hematological 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 post diagnosis, 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 70th 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 non-redundant 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.
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Available online 24 July 2021
Data source: Supplementary information, https://doi.org/10.1002/1878-0261.13055
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© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited