Abstract
Serum protein fingerprints associated with MGUS and MM and their changes in MM after autologous stem cell transplantation (MM-ASCT, day 100) remain unexplored. Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers (Proseek Multiplex, Olink), enhanced serum levels of Adrenomedullin (ADM, Pcorr= .0004), Growth differentiation factor 15 (GDF15, Pcorr= .003), and soluble Major histocompatibility complex class I-related chain A (sMICA, Pcorr= .023), all prosurvival and chemoprotective factors for myeloma cells, were detected in MM comparing to MGUS. Comparison of MGUS and healthy subjects revealed elevation of angiogenic and antia-poptotic midkine (Pcorr= .0007) and downregulation of Transforming growth factor beta 1 (TGFB1, Pcorr= .005) in MGUS. Importantly, altered serum pattern was associated with MM-ASCT compared to paired MM at the diagnosis as well as to healthy controls, namely by upregulated B-Cell Activating Factor (sBAFF) (Pcorr< .006) and sustained elevation of other pro-tumorigenic factors. In conclusion, the serum fingerprints of MM and MM-ASCT were characteristic by elevated levels of prosurvival and chemoprotective factors for myeloma cells.
Highlights
Monoclonal gammopathy of undetermined significance (MGUS) is a precursor lesion to overt multiple myeloma (MM), a clonal B-cell malignancy characterized by excessive multiplication of a plasma cell clone(s) in bone marrow, and accumulation of either a monoclonal immunoglobulin (Ig) (M-protein) or an Igfree light chain in blood [1]
Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers (Proseek Multiplex, Olink), enhanced serum levels of Adrenomedullin (ADM, Pcorr= .0004), Growth differentiation factor 15 (GDF15, Pcorr= .003), and soluble Major histocompatibility complex class I-related chain A, all prosurvival and chemoprotective factors for myeloma cells, were detected in MM comparing to MGUS
We investigated the complexity of serum microenvironment in MGUS, MM and MM after autologous stem cell transplantation (ASCT) using highly-sensitive PEA immunoassay
Summary
Monoclonal gammopathy of undetermined significance (MGUS) is a precursor lesion to overt multiple myeloma (MM), a clonal B-cell malignancy characterized by excessive multiplication of a plasma cell clone(s) in bone marrow, and accumulation of either a monoclonal immunoglobulin (Ig) (M-protein) or an Igfree light chain in blood [1]. Better characterization of neoplastic cells and microenvironment in particular myeloma stages is needed as well as clarifying of reason(s) for treatment failure in most MM patients [2, 3, 4]. The key role in microenvironment play bone marrow stromal cells and other microenvironmental cells that secrete a plethora of cytokines and growth factors after paracrine stimulation and/or direct interaction with neoplastic cells [7]
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