Proteomic Alteration in the Progression of Multiple Myeloma: A Comprehensive Review

Abstract

Multiple myeloma (MM) is an incurable hematologic malignancy. Most MM patients are diagnosed at a late stage because the early symptoms of the disease can be uncertain and nonspecific, often resembling other, more common conditions. Additionally, MM patients are commonly associated with rapid relapse and an inevitable refractory phase. MM is characterized by the abnormal proliferation of monoclonal plasma cells in the bone marrow. During the progression of MM, massive genomic alterations occur that target multiple signaling pathways and are accompanied by a multistep process involving differentiation, proliferation, and invasion. Moreover, the transformation of healthy plasma cell biology into genetically heterogeneous MM clones is driven by a variety of post-translational protein modifications (PTMs), which has complicated the discovery of effective treatments. PTMs have been identified as the most promising candidates for biomarker detection, and further research has been recommended to develop promising surrogate markers. Proteomics research has begun in MM, and a comprehensive literature review is available. However, proteomics applications in MM have yet to make significant progress. Exploration of proteomic alterations in MM is worthwhile to improve understanding of the pathophysiology of MM and to search for new treatment targets. Proteomics studies using mass spectrometry (MS) in conjunction with robust bioinformatics tools are an excellent way to learn more about protein changes and modifications during disease progression MM. This article addresses in depth the proteomic changes associated with MM disease transformation.

Transcriptional Remodeling of the Stromal and Endothelial Microenvironment in MGUS to Multiple Myeloma Progression

“…Interestingly, genes upregulated at the MGUS stage of the MIcγ1 model mirrored those elevated at the MM stage in the BIcγ1 model, supporting the rapid disease progression (supplemental Figure 6B). Likewise, we observed an increased vascular phenotype during the MGUS stage, along with the upregulation of Anxa2, Anxa5, S100a6, and S100a10 in MM genes associated with a more aggressive disease 24,25 (Figures S6C-F).…”

“…Interestingly, genes upregulated in MGUS-MIcγ1 EC mirrored those elevated in MM-BIcγ1 EC, showing an increased vascular phenotype and supporting the rapid disease progression of the MIcγ1 model (supplemental Figure 6B). Likewise, Anxa2, Anxa5, S100a6, and S100a10 were upregulated in MM-MIcγ1 EC, which have been associated with a more aggressive disease 24,25 (Figures S6C-F).…”

A study to identify novel biomarkers associated with multiple myeloma

“…While challenges such as standardization, data interpretation, and cost-effectiveness remain, ongoing advancements in proteomic technologies and bioinformatics are addressing these issues and fostering the integration of proteomic markers into clinical practice. Ultimately, the integration of proteomic markers into the management of multiple myeloma holds the potential to revolutionize the field by enabling more precise, personalized, and effective approaches to diagnosis and treatment, ultimately improving the quality of life and prognosis for individuals affected by this challenging disease [50].…”

TMT-Based Proteomics Analysis of Senescent Nucleus Pulposus from Patients with Intervertebral Disc Degeneration

“…Quantitative proteomics is a high-throughput screening technique commonly used to quantify proteins and metabolites in complex samples. It can be used to identify novel targets for disease treatment and elucidate the changes in target proteins involved in disease pathogenesis and drug interventions [14][15][16][17][18][19]. Tandem mass tag (TMT)-based proteomics technology has the advantages of high throughput, high sensitivity, good reproducibility, low systematic bias, and low noise.…”