scholarly journals Obesity as a Possible Risk Factor for Progression from Monoclonal Gammopathy of Undetermined Significance Progression into Multiple Myeloma: Could Myeloma Be Prevented with Metformin Treatment?

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Ademar Dantas da Cunha Júnior ◽  
Dalila Luciola Zanette ◽  
Fernando Vieira Pericole ◽  
Sara Teresinha Olalla Saad ◽  
José Barreto Campello Carvalheira
Keyword(s):  
Multiple Myeloma ◽  
Risk Factor ◽  
Inflammatory Cytokines ◽  
Monoclonal Gammopathy ◽  
Therapeutic Option ◽  
Epidemiological Studies ◽  
Cellular Level ◽  
Biological Pathways ◽  
Metformin Treatment ◽  
Undetermined Significance

Obesity is increasingly associated with the transformation of monoclonal gammopathy of undetermined significance (MGUS) into multiple myeloma (MM). Obesity, MGUS, and MM share common etiopathogenesis mechanisms including altered insulin axis and the action of inflammatory cytokines. Consistent with this interconnection, metformin could predominantly exert inhibition of these pathophysiological factors and thus be an attractive therapeutic option for MGUS. Despite the possible clinical significance, only a limited number of epidemiological studies have focused on obesity as a risk factor for MGUS and MM. This review describes multiple biological pathways modulated by metformin at the cellular level and their possible impacts on the biology of MGUS and its progression into MM.

Monosomy 13 Is Associated With the Transition of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma

Blood ◽  
1999 ◽  
Vol 94 (8) ◽  
pp. 2583-2589 ◽  
Author(s):  
Hervé Avet-Loiseau ◽  
Jian-Yong Li ◽  
Nadine Morineau ◽  
Thierry Facon ◽  
Christophe Brigaudeau ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Epidemiological Studies ◽  
Significant Difference ◽  
Chromosomal Changes ◽  
Cell Subpopulations ◽  
Undetermined Significance

Chromosomal abnormalities are present in most (if not all) patients with multiple myeloma (MM) and primary plasma cell leukemia (PCL). Furthermore, recent data have shown that numerical chromosomal changes are present in most individuals with monoclonal gammopathy of undetermined significance (MGUS). Epidemiological studies have shown that up to one third of MM may emerge from pre-existing MGUS. To clarify further possible stepwise chromosomal aberrations on a pathway between MGUS and MM, we have analyzed 158 patients with either MM or primary PCL and 19 individuals with MGUS using fluorescence in situ hybridization (FISH). Our FISH analyses were designed to detect illegitimate IGH rearrangements at 14q32 or monosomy 13. Whereas translocations involving the 14q32 region were observed with a similar incidence (60%) in both conditions, a significant difference was found in the incidence of monosomy 13 in MGUS versus MM or primary PCL. It was present in 40% of MM/PCL patients, but in only 4 of 19 MGUS individuals. Moreover, whereas monosomy 13 was found in the majority of plasma cells in MM, it was observed only in cell subpopulations in MGUS. It is noteworthy that, in a group of 20 patients with MM and a previous MGUS history, incidence of monosomy 13 was 70% versus 31% in MM patients without a known history of MGUS (P = .002). Thus, this study highlights monosomy 13 as correlated with the transformation of MGUS to overt MM and may define 2 groups of MM with possible different natural history and outcome, ie, post-MGUS MM with a very high incidence of monosomy 13 and de novo MM in which other genetic events might be involved. Serial analyses of individuals with MGUS will be needed to validate this model.

scholarly journals Comparison of Monoclonal Gammopathies Linked to Poliovirus or Coxsackievirus vs. Other Infectious Pathogens

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 438
Author(s):  
Jean Harb ◽  
Nicolas Mennesson ◽  
Cassandra Lepetit ◽  
Maeva Fourny ◽  
Margaux Louvois ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Coat Proteins ◽  
Chronic Stimulation ◽  
B Cell Epitopes ◽  
Monoclonal Immunoglobulins ◽  
Self Antigen ◽  
Coxsackievirus B1 ◽  
Undetermined Significance

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.

scholarly journals Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Sæmundur Rögnvaldsson ◽  
Thorvardur Jon Love ◽  
Sigrun Thorsteinsdottir ◽  
Elín Ruth Reed ◽  
Jón Þórir Óskarsson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Early Treatment ◽  
Monoclonal Gammopathy ◽  
Controlled Trial ◽  
Participation Rate ◽  
Population Based ◽  
Early Therapy ◽  
Screening Study ◽  
Undetermined Significance

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.

Interleukin‐6 is expressed by plasma cells from patients with multiple myeloma and monoclonal gammopathy of undetermined significance

1998 ◽  
Vol 101 (2) ◽  
pp. 287-295 ◽  
Author(s):  
Hamdi I. A. Sati ◽  
Jane F. Apperley ◽  
Mike Greaves ◽  
John Lawry ◽  
Roger Gooding ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Interleukin 6 ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Undetermined Significance

scholarly journals Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma

Blood ◽  
2008 ◽  
Vol 112 (9) ◽  
pp. 3582-3586 ◽  
Author(s):  
Sigurdur Y. Kristinsson ◽  
Thomas R. Fears ◽  
Gloria Gridley ◽  
Ingemar Turesson ◽  
Ulf-Henrik Mellqvist ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
First Year ◽  
Small Hospital ◽  
Entire Study ◽  
Crude Incidence ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
Undetermined Significance

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.

scholarly journals Association of Immune Marker Changes With Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma

JAMA Oncology ◽  
2019 ◽  
Vol 5 (9) ◽  
pp. 1293 ◽  
Author(s):  
Ola Landgren ◽  
Jonathan N. Hofmann ◽  
Charlene M. McShane ◽  
Loredana Santo ◽  
Malin Hultcrantz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Immune Marker ◽  
Undetermined Significance

scholarly journals Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study

Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5412-5417 ◽  
Author(s):  
Ola Landgren ◽  
Robert A. Kyle ◽  
Ruth M. Pfeiffer ◽  
Jerry A. Katzmann ◽  
Neil E. Caporaso ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Population Based ◽  
Serum Samples ◽  
M Proteins ◽  
Cancer Screening Trial ◽  
Risk Of Progression ◽  
Study Population ◽  
A Prospective Study ◽  
Undetermined Significance

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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