Presentation
Abstract 780: Molecular chaperone is a novel biomarker for disease outcome in multiple myeloma
Experimental and Molecular Therapeutics
(2018)
Abstract
Multiple myeloma (MM) is an incurable plasma cell neoplasm whose pathogenesis is closely linked to dysregulated unfolded protein response (UPR) in the endoplasmic reticulum (ER). MM typically evolves from an asymptomatic premalignant stage called monoclonal gammopathy of undetermined significance (MGUS), to an intermediate asymptomatic smoldering MM (SMM), to eventually symptomatic MM. However, no single pathologic or molecular biomarker can be used to distinguish MM patients from SMM, who have clonal premalignant plasma cells from those with clonal myeloma cells. Therefore, there is a compelling need for further development of novel diagnosis and prognosis biomarkers for MM. Heat shock protein grp94 is a key downstream chaperone in the ER to mediate UPR. Using genetic approaches, we have demonstrated that grp94 is an obligate chaperone for Wnt co-receptor low-density lipoprotein receptor-related protein 6 and that it is required for multiple myeloma cell survival, which is mediated in part by the Wnt target survivin. Moreover, we found that grp94 is highly expressed in malignant plasma cells in MM, and the higher level of grp94 is significantly associated with more advanced stage of this disease. Additionally, the grp94 expression is significantly associated with the levels of serum M protein in MM patients, but not in patients with MGUS and SMM. Thus, our studies demonstrated that molecular chaperone grp94 is a novel diagnostic and prognostic biomarker for MM as well as a potential target for treatment of this disease.
Publication Date
July 1, 2018
DOI
10.1158/1538-7445.am2018-780
Citation Information
1. Li Y, Zhang PL, Li Z, Liu B. Abstract 780: Molecular chaperone is a novel biomarker for disease outcome in multiple myeloma. Cancer Res [Internet]. 2018;78(13):780. Available from: http://cancerres.aacrjournals.org/content/78/13_Supplement/780.abstract