, multiple myeloma, MGUS

OBJECTIVES: Our objective was to shorten the screen for multiple myeloma (MM), through reflex testing. DESIGN AND METHODS: The clinical laboratory in the public University Hospital of San Juan (Alicante, Spain), serves 234,551 inhabitants. Through an intervention agreed with general practitioners, the Laboratory Information System (LIS) automatically registered serum immunoglobulins (Ig) when serum total proteins (STP) > 80 g/L for the first time in primary care patients...

Gastrointestinal involvement in amyloidosis is reported in 3% of cases, mostly associated with multiple myeloma. An elderly man with chronic kidney disease presented to the hospital after a large melenic bowel movement. The patient was tachycardic and anemic to 3.8 g/dL on admission and was transfused blood. Endoscopy and colonoscopy were unremarkable. Subsequently, the patient had 2 more admissions for severe anemia requiring blood transfusion. Repeat esophagoduodenoscopy with capsule endoscopy were unremarkable...

BACKGROUND: The aggregation of clonal plasma cells causes plasma cell neoplasms, which vary in severity and clinical outcomes. The present research focused on the epidemiological, clinical, immunologic, and cytogenetic characteristics of plasma cell neoplasms. METHODS: In this five-year retrospective cross-sectional study, demographic information such as age and sex, calcium elevation, renal insufficiency, anemia, and bone lesion (CRAB) characteristics, as well as laboratory data including bone marrow and peripheral blood film results, immunohistochemistry, flow cytometry, and cytogenetic study outcomes were collected at Shiraz University of Medical Sciences, Shiraz, Iran...

Multiple myeloma (MM) is a heterogeneous disease with survival ranging from months to decades. The goal of 'cure' remains elusive for most patients, but has been shown to be possible, with durable remission and a transition to a plateau phase (analogous to monoclonal gammopathy of uncertain significance/smoldering Myeloma (MGUS/SMM)). Two representative cases set the stage to illustrate how this might be possible and what still needs to be determined to achieve functional disease control over a prolonged period...

With the advent of outperforming and massive laboratory tools, such as multiparameter flow cytometry and next-generation sequencing, hematopoietic cell clones with putative abnormalities for a variety of blood malignancies have been appreciated in otherwise healthy individuals. These conditions do not fulfill the criteria of their presumed cancer counterparts, and thus have been recognized as their precursor states. This is the case of monoclonal gammopathy of unknown significance (MGUS), the first blood premalignancy state described, preceding multiple myeloma (MM) or Waldenström macroglobulinemia (WM)...

Multiple myeloma (MM) is a cancer of plasma cells. Normal (NL) cells are considered to pass through a precancerous state, such as monoclonal gammopathy of undetermined significance (MGUS), before transitioning to MM. In the present study, we acquired Raman spectra at three stages-834 NL, 711 MGUS, and 970 MM spectra-and applied the dynamical network biomarker (DNB) theory to these spectra. The DNB analysis identified MGUS as the unstable pre-disease state of MM and extracted Raman shifts at 1149 and 1527-1530 cm-1 as DNB variables...

Multiple myeloma is a largely incurable and life-threatening malignancy of antibody-secreting plasma cells. An effective and widely available animal model that recapitulates human myeloma and related plasma cell disorders is lacking. We show that busulfan-conditioned hIL-6 transgenic NSG mice (NSG+hIL6) reliably support the engraftment of malignant and pre-malignant human plasma cells including from patients diagnosed with monoclonal gammopathy of undetermined significance, pre- and post-relapse myeloma, plasma cell leukemia, and AL amyloidosis...

BACKGROUND: High levels of physical activity are associated with reduced risk of the blood cancer multiple myeloma (MM). MM is preceded by the asymptomatic stages of monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM) which are clinically managed by watchful waiting. A case study (N = 1) of a former elite athlete aged 44 years previously indicated that a multi-modal exercise programme reversed SMM disease activity. To build from this prior case study, the present pilot study firstly examined if short-term exercise training was feasible and safe for a group of MGUS and SMM patients, and secondly investigated the effects on MGUS/SMM disease activity...

BACKGROUND: Clarkson's disease is a very rare entity characterised by acute episodes of systemic oedema and severe hypotension associated with paraproteinaemia. Its classical treatment relies on methylxanthine combined with terbutaline. Although this prophylactic therapy reduces the mortality rate, relapses are frequent. Eighty percent of patients with Clarkson's disease present with monoclonal gammopathy of unknown significance (MGUS). The risk of progression to multiple myeloma is 1% per year...

Multiple Myeloma (MM) is a plasma cell cancer with high mortality and morbidity rates. Its incidence rate has increased by 143% since 1975. Adipokines, cytokines, chemokines, and genetic variations influence the development and progression of MM. Chromosomal translocations cause mutations associated with MM. The pathogenesis of MM is complicated by novel issues like miRNAs, RANKL, Wnt/DKK1, Wnt, and OPG. Conventional diagnosis methods include bone marrow biopsy, sPEP or uPEP, sIFE and uIFE, and sFLC assay, along with advanced techniques such as FISH, SNPA, and gene expression technologies...

The hallmark of multiple myeloma (MM) is a clonal plasma cell infiltration in the bone marrow accompanied by myelosuppression and osteolysis. Premalignant stages like monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic stages like smoldering myeloma (SMM) can progress to multiple myeloma (MM). Mesenchymal stromal cells (MSC) are an integral component of the bone marrow microenvironment and play an important role for osteoblast differentiation and hematopoietic support. While stromal alterations have been reported in MM contributing to hematopoietic insufficiency and osteolysis, it is not clear whether alterations in MSC already occur in MGUS or SMM...

Multiple Myeloma (MM) is the second most common hematological malignancy and is characterized by clonal expansion of malignant plasma cells in the bone marrow. In spite of recent advances in the field of MM, the disease has remained incurable. MM is preceded by a premalignant state known as monoclonal gammopathy of undetermined significance (MGUS), with a risk of progression to MM of 1% per year. Establishing a scalable approach that refines the identification of MGUS patients at high risk of progression to MM can transform the clinical management of the disease, improve the patient's quality of life, and will have significant socioeconomic implications...

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BACKGROUND: As the second most prevalent hematologic malignancy, multiple myeloma (MM) affects plasma cells and is characterized by chromosomal abnormalities, particularly involving the immunoglobulin heavy chain switch region. MM represents a biologically and clinically heterogeneous hematological malignancy that serves as a clonal evolution model, exhibiting clonal heterogeneity throughout all stages from monoclonal gammopathy undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to MM...

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma with few known risk factors. The emergence of mass spectrometry (MS) for the detection of MGUS has provided new opportunities to evaluate its risk factors. 2628 individuals at elevated risk for multiple myeloma were enrolled in a screening study and completed an exposure survey (PROMISE; ClinicalTrials.gov, #NCT03689595). Participant samples were screened by MS, and monoclonal proteins (M-proteins) with concentrations >0...

There is some evidence that a prior cancer is a risk factor for the development of multiple myeloma (MM). If this is true, prior cancer should be associated with higher prevalence or increased progression rate of monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM and related disorders. Those with a history of cancer might therefore present a target population for MGUS screening. This two-part study is the first study to evaluate the relationship of MGUS and prior cancers. First, we evaluated whether prior cancers were associated with having MGUS at the time of screening in the Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM) study that includes 75,422 individuals screened for MGUS...

The Lymphocyte-Activation Protein 3 (LAG-3) inhibitory receptor is expressed on regulatory plasma cells (PCs). Micro-environmental cells that express LAG-3 were found to be increased during the progression of smoldering multiple myeloma (SMM). To assess the possible role of LAG-3 expression on regulatory PCs in patients with plasma cell dyscrasia. Purified Cluster of Differentiation 138 (CD138+) PCs from patients with premalignant conditions, active multiple myeloma (MM), and controls were analyzed for the expression of LAG-3 by flow cytometry...

Multiple myeloma is a malignancy of bone-marrow-localized, isotype-switched plasma cells that secrete a monoclonal immunoglobulin and cause hyperCalcemia, Anemia, Renal failure, and lytic Bone disease. It is preceded, often for decades, by a relatively stable monoclonal gammopathy lacking these clinical and malignant features. Both conditions are characterized by the presence of types of immunoglobulin heavy gene translocations that dysregulate a cyclin D family gene on 11q13 (CCND1), 6p21 (CCND3), or 12q11 (CCND2), a maf family gene on 16q23 (MAF), 20q11 (MAFB), or 8q24 (MAFA), or NSD2/FGFR3 on 4p16, or the presence of hyperdiploidy...

This research indicates that monoclonal gammopathy of undetermined significance (MGUS) and myeloma may stem from chronic immune activation and inflammation, causing immune dysfunction and spatial immune exclusion. As the conditions progress, a shift toward myeloma involves ongoing immune impairment, affecting both innate and adaptive immunity. Intriguingly, even in advanced myeloma stages, susceptibility to immune effector cells persists. This insight highlights the intricate interplay between immune responses and the development of these conditions, paving the way for potential therapeutic interventions targeting immune modulation in the management of MGUS and myeloma...

BACKGROUND: Multiple myeloma (MM) is a hematological malignancy that develops over years from the asymptomatic precursors, monoclonal gammopathy of undetermined significance, and smoldering multiple myeloma. Recent evidence shows that by initiating treatment at an asymptomatic stage, outcomes in MM can be significantly improved. However, a vast majority of MM patients are diagnosed after the development of symptomatic end-organ damage and cannot reap the benefits of early treatment. The precursors of MM are easily detected by serum protein electrophoresis and free light chain assay of the serum, raising the question of whether population-based screening could detect MM at an asymptomatic stage and significantly expand the availability of early treatment in MM...