Monoclonal Gammopathy of Undetermined Significance: A Comprehensive Review

Kaur, Jasneet; Valisekka, Sai Sudha; Hameed, Maha; Bandi, Pushyami Satya; Varma, Samyuktha; Onwughalu, Chibuzor Joseph; Ibrahim, Hany M.; Mongia, Himani

doi:10.1016/j.clml.2023.02.004

Cited by 5 publications

(1 citation statement)

References 170 publications

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“…Nevertheless, most patients develop drug resistance and eventually die from the disease. The etiology of MM is poorly understood, but almost all cases are preceded by an asymptomatic pre-malignant disorder called Monoclonal Gammopathy of Undetermined Significance (MGUS) [4]. MGUS occurs in ~ 3% of the population over the age of 50 and 5% over the age of 70, and incidence increases with advancing age.…”

Section: Introductionmentioning

confidence: 99%

Progression of monoclonal gammopathy of undetermined significance to multiple myeloma is associated with enhanced translational quality control and overall loss of surface antigens

Ravn Berg,

Dikic,

Sharma

et al. 2024

J Transl Med

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Background Despite significant advancements in treatment strategies, multiple myeloma remains incurable. Additionally, there is a distinct lack of reliable biomarkers that can guide initial treatment decisions and help determine suitable replacement or adjuvant therapies when relapse ensues due to acquired drug resistance. Methods To define specific proteins and pathways involved in the progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM), we have applied super-SILAC quantitative proteomic analysis to CD138 + plasma cells from 9 individuals with MGUS and 37 with MM. Results Unsupervised hierarchical clustering defined three groups: MGUS, MM, and MM with an MGUS-like proteome profile (ML) that may represent a group that has recently transformed to MM. Statistical analysis identified 866 differentially expressed proteins between MM and MGUS, and 189 between MM and ML, 177 of which were common between MGUS and ML. Progression from MGUS to MM is accompanied by upregulated EIF2 signaling, DNA repair, and proteins involved in translational quality control, whereas integrin- and actin cytoskeletal signaling and cell surface markers are downregulated. Conclusion Compared to the premalignant plasma cells in MGUS, malignant MM cells apparently have mobilized several pathways that collectively contribute to ensure translational fidelity and to avoid proteotoxic stress, especially in the ER. The overall reduced expression of immunoglobulins and surface antigens contribute to this and may additionally mediate evasion from recognition by the immune apparatus. Our analyses identified a range of novel biomarkers with potential prognostic and therapeutic value, which will undergo further evaluation to determine their clinical significance.

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Section: Introductionmentioning

confidence: 99%

Progression of monoclonal gammopathy of undetermined significance to multiple myeloma is associated with enhanced translational quality control and overall loss of surface antigens

Ravn Berg,

Dikic,

Sharma

et al. 2024

J Transl Med

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Clinical significance of FLC tests in patients without other evidence of hematologic disorder

Shpitzer,

Cohen,

Perry

et al. 2024

Clin Exp Med

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The systemic capillary leak syndrome following COVID-19 vaccine

Zhao,

Xue,

Zhao

et al. 2024

Human Vaccines & Immunotherapeutics

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The COVID-19 outbreak has been declared the sixth Public Health Emergency of International Concern certified by the World Health Organization. With the extensive application of COVID-19 vaccines, rare but serious adverse reactions have gradually emerged, among which systemic capillary leak syndrome (SCLS) deserves our attention. SCLS is difficult to diagnose. Not only can it exacerbate various diseases, but also can lead to pulmonary edema, kidney failure, and even death. We summarized and discussed case reports of SCLS induced by COVID-19 vaccines to raise awareness of COVID-19 vaccine-associated rare diseases. We conducted a comprehensive search in Web of Science, PubMed and Embase and collected case reports of SCLS induced by COVID-19 vaccine before February 19, 2024. We identified and analyzed 12 articles, encompassing 15 cases. We synthesized the data to summerize possible mechanisms of SCLS, clinical manifestations, differential diagnoses, and therapeutic approaches. Most SCLS occurred after vaccination with the Pfe-Biontech mRNA vaccine (9/15) and following the second vaccination (10/15). Almost all patients experienced hypotension (13/15) and tachycardia (11/15). Most patients received intravenous fluids (9/15) and corticosteroids (9/15). 11 patients were recovered and were discharged, while 4 patients died. Inflammation and endothelial cell damage may be linked to SCLS and COVID-19 vaccines. These findings highlight the necessity of focusing on serious adverse reactions of COVID-19 vaccines and the urgency to reconsider the safety of COVID-19 vaccines.

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Monoclonal Gammopathy of Undetermined Significance: A Comprehensive Review

Cited by 5 publications

References 170 publications

Progression of monoclonal gammopathy of undetermined significance to multiple myeloma is associated with enhanced translational quality control and overall loss of surface antigens

Progression of monoclonal gammopathy of undetermined significance to multiple myeloma is associated with enhanced translational quality control and overall loss of surface antigens

Clinical significance of FLC tests in patients without other evidence of hematologic disorder

The systemic capillary leak syndrome following COVID-19 vaccine

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