scholarly journals Monoclonal gammopathy of undetermined significance

Blood ◽  
2019 ◽  
Vol 133 (23) ◽  
pp. 2484-2494 ◽  
Author(s):  
Tarek H. Mouhieddine ◽  
Lachelle D. Weeks ◽  
Irene M. Ghobrial

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell dyscrasia that consistently precedes multiple myeloma (MM) with a 1% risk of progression per year. Recent advances have improved understanding of the complex genetic and immunologic factors that permit progression from the aberrant plasma cell clone to MGUS and overt MM. Additional evidence supports bidirectional interaction of MGUS cells with surrounding cells in the bone marrow niche that regulates malignant transformation. However, there are no robust prognostic biomarkers. Herein we review the current body of literature on the biology of MGUS and provide a rationale for the improved identification of high-risk MGUS patients who may be appropriate for novel clinical interventions to prevent progression or eradicate premalignant clones prior to the development of overt MM.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1801-1801
Author(s):  
Johannes Drach ◽  
Astrid Slany ◽  
Thomas Mohr ◽  
Johannes Griss ◽  
Christoph C Zielinski ◽  
...  

Abstract Abstract 1801 Poster Board I-827 The microenvironment of tumor cells in the bone marrow was demonstrated to contribute to tumor promotion and survival. The role of bone marrow fibroblasts (BMFs) in supporting the malignant plasma cell clone in multiple myeloma (MM) has been established, but it remains unclear to which extent the BM microenvironment in general and BMFs in particular are involved in the progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. Therefore we performed proteomics studies on the secretome of BMFs isolated from healthy donors, patients suffering from MGUS and patients suffering from MM. Compared to normal background, BMFs derived from MGUS secreted elevated levels of proteins indicating mitogenic activity and moderate inflammation. These proteins included periostin, IL-6, CXCL5 and CSF-1. Insulin-like growth factor II, which is normally not expressed by normal BMFs, was secreted by BMF cells derived from MGUS as well as from MM. In addition to those and other proteins, BMF cells derived from MM were found to specifically secrete stem cell growth factor, MMP-28 and stanniocalcin-1. These data indicate a step-wise alteration of BMF secretion activity related to the stage of the underlying plasma cell dyscrasia. Therefore BMF might support the progression from MGUS to MM. In order to correlate the secretion performance of BMF with blood serum levels of candidate marker proteins, Luminex assays are employed. Based upon these results, it is our aim to identify serum biomarkers which allow to assess the functional state of BMF and thus the risk for the progression of MGUS to MM. Disclosures No relevant conflicts of interest to declare.


2015 ◽  
Vol 5 (3) ◽  
pp. 180-186 ◽  
Author(s):  
Jin Hae Kim ◽  
Ji Won Kim ◽  
Young Nam Kim ◽  
Hye In Kim ◽  
Jun Young Kim ◽  
...  

Monoclonal gammopathy with undetermined significance (MGUS) carries a risk of progression to multiple myeloma, and progression is usually diagnosed with changes in M-protein or bone marrow biopsy. We report a case of 62-year-old female patient showing MGUS progression to multiple myeloma without significant changes in M-protein but diagnosed by kidney biopsy. During the follow-ups, azotemia and tubular proteinuria were aggravated without elevation of M-protein. Kidney biopsy showed intratubular and glomerular inclusions associated with plasma cell dysplasia. The progression of MGUS to multiple myeloma was diagnosed by this kidney biopsy. The patient's renal function and tubular proteinuria were markedly improved after chemotherapy.


Author(s):  
Vui Yung Chieng ◽  
Rod Sampson

Monoclonal gammopathy of undetermined significance is a premalignant, plasma cell disorder. Due to the potential risk of progression to multiple myeloma or a plasma cell-related disorder, it is important for GPs to recognise and manage patients in this cohort appropriately. This article aims to improve understanding, recognition and management of these patients in primary care.


Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 166-171 ◽  
Author(s):  
PR Greipp ◽  
RA Kyle

We reviewed the clinical and morphological findings in 43 cases of monoclonal gammopathy of undetermined significance (MGUS), 9 of smoldering multiple myeloma (SMM), and 23 of overt multiple myeloma (MM). In all cases, the patients' physicians had requested a bone marrow examination because of the possibility of MM. In all 75 cases, 3H-thymidine labeling indices were performed. The plasma cell labeling index correctly classified 62 of the 75 cases (83%). A linear discriminant function combining the labeling index and percentage of plasma cells improved the accuracy to 92% (69/75), or to 95% (71/75) if patients in whom MM developed within 6 mo were considered to have MM. The labeling index was most critical for the differential diagnosis of MM from SMM (p less than 0.001). Serum or urine M-protein level, percentage of plasma cells or lymphocytes in the bone marrow, and plasma cell grade, asynchrony, and nucleolar size failed to discriminate the group with SMM from the group with MM. In patients with MGUS or SMM, a plasma cell labeling index greater than 0.4% warned of impending MM. The plasma cell labeling index is a reliable diagnostic test when applied in cases of monoclonal gammopathy, especially when differentiation from MM is difficult using standard clinical criteria.


Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 166-171 ◽  
Author(s):  
PR Greipp ◽  
RA Kyle

Abstract We reviewed the clinical and morphological findings in 43 cases of monoclonal gammopathy of undetermined significance (MGUS), 9 of smoldering multiple myeloma (SMM), and 23 of overt multiple myeloma (MM). In all cases, the patients' physicians had requested a bone marrow examination because of the possibility of MM. In all 75 cases, 3H-thymidine labeling indices were performed. The plasma cell labeling index correctly classified 62 of the 75 cases (83%). A linear discriminant function combining the labeling index and percentage of plasma cells improved the accuracy to 92% (69/75), or to 95% (71/75) if patients in whom MM developed within 6 mo were considered to have MM. The labeling index was most critical for the differential diagnosis of MM from SMM (p less than 0.001). Serum or urine M-protein level, percentage of plasma cells or lymphocytes in the bone marrow, and plasma cell grade, asynchrony, and nucleolar size failed to discriminate the group with SMM from the group with MM. In patients with MGUS or SMM, a plasma cell labeling index greater than 0.4% warned of impending MM. The plasma cell labeling index is a reliable diagnostic test when applied in cases of monoclonal gammopathy, especially when differentiation from MM is difficult using standard clinical criteria.


Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5412-5417 ◽  
Author(s):  
Ola Landgren ◽  
Robert A. Kyle ◽  
Ruth M. Pfeiffer ◽  
Jerry A. Katzmann ◽  
Neil E. Caporaso ◽  
...  

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma-cell proliferative disorder associated with a life-long risk of progression to multiple myeloma (MM). It is not known whether MM is always preceded by a premalignant asymptomatic MGUS stage. Among 77 469 healthy adults enrolled in the nationwide population-based prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 71 subjects who developed MM during the course of the study in whom serially collected (up to 6) prediagnostic serum samples obtained 2 to 9.8 years prior to MM diagnosis were available. Using assays for monoclonal (M)–proteins (electrophoresis/immunofixation) and kappa-lambda free light chains (FLCs), we determined longitudinally the prevalence of MGUS and characterized patterns of monoclonal immunoglobulin abnormalities prior to MM diagnosis. MGUS was present in 100.0% (87.2%-100.0%), 98.3% (90.8%-100.0%), 97.9% (88.9%-100.0%), 94.6% (81.8%-99.3%), 100.0% (86.3%-100.0%), 93.3% (68.1%-99.8%), and 82.4% (56.6%-96.2%) at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In approximately half the study population, the M-protein concentration and involved FLC-ratio levels showed a yearly increase prior to MM diagnosis. In the present study, an asymptomatic MGUS stage consistently preceded MM. Novel molecular markers are needed to better predict progression to MM in patients with MGUS.


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