Serum β2-microglobulin levels in multiple myeloma and monoclonal gammapathy of undetermined significance: A clinical study of 55 patients

1986 ◽  
Vol 16 (1) ◽  
pp. 53-58
Author(s):  
Giovanni Chelazzi ◽  
Giorgio Senaldi
2018 ◽  
Vol 72 ◽  
pp. 953-965
Author(s):  
Anna Suska ◽  
Artur Jurczyszyn

Multiple myeloma (MM) accounts for about 13% of haematological malignancies. Etiopathogenesis is still not fully understood. Confirmed risk factors include the following: age, male sex, black race and MM among first-degree relatives. MM may be preceded by monoclonal gammapathy of undetermined significance (MGUS). The risk of progression is about 1% per year. Genetic changes, proinflammatory and proangiogenic cytokines and some infections may play a role in this risk. With regard to lifestyle risk factors, only obesity and overweight were associated with increased MM incidence and elevated risk for transformation of MGUS to MM. Regarding occupational exposure, there is an increased risk of MM among farmers, firefighters and hairdressers. As far as autoimmune diseases are concerned, only ankylosing spondylitis and pernicious anemia are associated with significantly increased MM risk. Increased risk of MM was also reported in relatives of MM patients, especially in first-degree relatives and in African-American families. The risk of MGUS is elevated in both first-degree relatives of MM and MGUS patients. Data from genetic analysis indicated translocations involving immunoglobulin heavy chain (IGH) loci, hyperphosphorylation of several proteins which are the targets for paraproteins produced by malignant plasma cells and single nucleotide polymorphisms (susceptibility loci) as the potential genetic predisposition to multiple myeloma. The mechanism of heterogeneity of clinical manifestations of MM is not known. Anemia is less frequent in patients whose relatives were diagnosed with hematologic malignancy compared to those with a negative family history. In patients from a younger age group, osteolytic bone lesions were more common than in older patients. In conclusion, environmental exposures modify the genetic predisposition to MM and MGUS.


Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 438
Author(s):  
Jean Harb ◽  
Nicolas Mennesson ◽  
Cassandra Lepetit ◽  
Maeva Fourny ◽  
Margaux Louvois ◽  
...  

Chronic stimulation by infectious pathogens or self-antigen glucosylsphingosine (GlcSph) can lead to monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Novel assays such as the multiplex infectious antigen microarray (MIAA) and GlcSph assays, permit identification of targets for >60% purified monoclonal immunoglobulins (Igs). Searching for additional targets, we selected 28 purified monoclonal Igs whose antigen was not represented on the MIAA and GlcSph assays; their specificity of recognition was then analyzed using microarrays consisting of 3760 B-cell epitopes from 196 pathogens. The peptide sequences PALTAVETG and PALTAAETG of the VP1 coat proteins of human poliovirus 1/3 and coxsackievirus B1/B3, respectively, were specifically recognized by 6/28 monoclonal Igs. Re-analysis of patient cohorts showed that purified monoclonal Igs from 10/155 MGUS/SM (6.5%) and 3/147 MM (2.0%) bound to the PALTAVETG or PALTAAETG epitopes. Altogether, PALTAV/AETG-initiated MGUS are not rare and few seem to evolve toward myeloma.


2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Sæmundur Rögnvaldsson ◽  
Thorvardur Jon Love ◽  
Sigrun Thorsteinsdottir ◽  
Elín Ruth Reed ◽  
Jón Þórir Óskarsson ◽  
...  

AbstractMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.


1998 ◽  
Vol 101 (2) ◽  
pp. 287-295 ◽  
Author(s):  
Hamdi I. A. Sati ◽  
Jane F. Apperley ◽  
Mike Greaves ◽  
John Lawry ◽  
Roger Gooding ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (9) ◽  
pp. 3582-3586 ◽  
Author(s):  
Sigurdur Y. Kristinsson ◽  
Thomas R. Fears ◽  
Gloria Gridley ◽  
Ingemar Turesson ◽  
Ulf-Henrik Mellqvist ◽  
...  

Patients with multiple myeloma (MM) have an increased risk of deep venous thrombosis (DVT), particularly when treated with immunomodulatory drugs. Recently, 2 small hospital-based studies observed persons with the MM precursor condition, monoclonal gammopathy of undetermined significance (MGUS), to be at increased risk of developing DVT. Among 4 196 197 veterans hospitalized at least once at US Veterans Affairs hospitals, we identified a total of 2374 cases of MGUS, and 39 272 persons were diagnosed with DVT (crude incidence 0.9 per 1000 person-years). A total of 31 and 151 DVTs occurred among MGUS and MM patients, respectively (crude incidence 3.1 and 8.7 per 1000 person-years, respectively; P < .01). Compared with the entire study population, the relative risk (RR) of DVT after a diagnosis of MGUS and MM was 3.3 (95% confidence interval [CI], 2.3-4.7) and 9.2 (95% CI, 7.9-10.8), respectively. The most prominent excess risk of DVT was found during the first year after diagnosis of MGUS (RR = 8.4; 95% CI, 5.7-12.2) and MM (RR = 11.6; 95% CI, 9.2-14.5). Among 229 MGUS cases (9.5%) that progressed to MM, only one person had a DVT diagnosis before transformation. Our findings suggest the operation of shared underlying mechanisms causing coagulation abnormalities among patients with MGUS and MM.


JAMA Oncology ◽  
2019 ◽  
Vol 5 (9) ◽  
pp. 1293 ◽  
Author(s):  
Ola Landgren ◽  
Jonathan N. Hofmann ◽  
Charlene M. McShane ◽  
Loredana Santo ◽  
Malin Hultcrantz ◽  
...  

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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