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1.
Cancer Imaging ; 24(1): 93, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992707

RESUMO

BACKGROUND: Dynamic contrast-enhanced-MRI (DCE-MRI) is able to study bone marrow angiogenesis in patients with multiple myeloma (MM) and asymptomatic precursor diseases but its role in the management of MM has not yet been established. The aims of this prospective study was to compare DCE-MRI-based parameters between all monoclonal plasma cell disease stages in order to find out discriminatory parameters and to seek correlations with other diffusion-weighted MRI and positron emission tomography (PET)-based biomarkers in a hybrid simultaneous whole-body-2-[18F]fluorodeoxyglucose (FDG)-PET/MRI (WB-2-[18F]FDG-PET/MRI) imaging approach. METHODS: Patients with newly diagnosed Monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) or symptomatic MM according to international myeloma working group and underwent WB-2-[18F]FDG-PET/MRI imaging including bone marrow DCE sequences at the Nantes University Hospital were prospectively enrolled in this study before receiving treatment. RESULTS: One hundred and sixty-seven patients (N = 167, mean age: 64 years ± 11 [Standard deviation], 66 males) were considered for the analysis. DCE-MRI-based Peak Enhancement Intensity (PEI), Time to PEI (TPEI) and their maximum intensity time ratio (MITR: PEI/TPEI) values were significantly different between the different monoclonal plasma cell disease stages, PEI values increasing and TPEI values decreasing progressively along the spectrum of plasma cell disorders, from MGUS stage to symptomatic multiple myeloma. PEI values were significantly higher in patients with diffuse bone marrow involvement (either in PET or in MRI images) than in those without diffuse bone marrow involvement, unlike TPEI values. PEI and TPEI values were not significantly different between patients with or without focal bone lesions. CONCLUSION: Different DCE-MRI-based parameters (PEI, TPEI, MITR) could significantly differentiate all monoclonal plasma cell disease stages and complemented conventional MRI and PET-based biomarkers.


Assuntos
Imagem de Difusão por Ressonância Magnética , Fluordesoxiglucose F18 , Mieloma Múltiplo , Tomografia por Emissão de Pósitrons , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Mieloma Múltiplo/diagnóstico por imagem , Estudos Prospectivos , Imagem de Difusão por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Imageamento por Ressonância Magnética/métodos , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico por imagem , Meios de Contraste , Imagem Multimodal/métodos , Compostos Radiofarmacêuticos , Imagem Corporal Total/métodos , Idoso de 80 Anos ou mais , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia
2.
Zhonghua Xue Ye Xue Za Zhi ; 45(4): 313-321, 2024 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-38951057

RESUMO

Flow cytometry plays an important role in the diagnosis and treatment of plasma cell diseases, particularly in the detection of circulating plasma cells (CPCs) in the peripheral blood. A consensus about the normalized use of flow cytometry in detection of CPCs in peripheral blood in clinical practice has been achieved. This consensus is founded on evidence-based principles, which elucidates the timing and value of flow cytometry for the detection of CPCs in the monoclonal gammopathy of undetermined significance, smoldering myeloma, multiple myeloma, and plasma cell leukemia and standardizes flow cytometry in the detection of CPCs in plasma cell diseases.


Assuntos
Citometria de Fluxo , Mieloma Múltiplo , Plasmócitos , Citometria de Fluxo/métodos , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/sangue , China , Paraproteinemias/diagnóstico , Paraproteinemias/sangue , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/sangue , Consenso , População do Leste Asiático
3.
Eur Rev Med Pharmacol Sci ; 28(12): 3880-3887, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38946385

RESUMO

OBJECTIVE: Monoclonal gammopathy of undetermined significance (MGUS) is a preneoplastic disease that often precedes multiple myeloma. The multistep evolutionary pattern of multiple myeloma is driven by genetic instability, a pro-inflammatory and immunosuppressive microenvironment, and tumor growth. Inflammation has long been recognized as a factor in both the onset and progression of cancer. PATIENTS AND METHODS: In this study, interleukin-18 plasma levels were compared in patients with multiple myeloma and monoclonal gammopathy of undetermined significance, as well as in a group of healthy controls. RESULTS: Our study shows that monoclonal gammopathy of undetermined significance patients have lower levels of interleukin-18 than healthy controls (521.657 ± 168.493 pg/ml vs. 1,266.481 ± 658.091 pg/ml for controls, p < 0.001). Thus, we discovered a significant difference in interleukin-18 levels between multiple myeloma patients and controls (418.177 ± 197.837 pg/ml; p = 0.001). CONCLUSIONS: In our work, we identified a reduction of interleukin-18 in monoclonal gammopathies. Furthermore, in this paper, we aimed to evaluate the existing literature on the potential mechanisms of action of this pro-inflammatory cytokine in the development of these diseases.


Assuntos
Interleucina-18 , Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Humanos , Interleucina-18/sangue , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/imunologia , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos de Casos e Controles
4.
J Transl Med ; 22(1): 548, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849800

RESUMO

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.


Assuntos
Progressão da Doença , Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Gamopatia Monoclonal de Significância Indeterminada/imunologia , Proteômica , Masculino , Feminino , Biossíntese de Proteínas , Pessoa de Meia-Idade , Idoso , Análise por Conglomerados , Plasmócitos/imunologia , Plasmócitos/patologia , Plasmócitos/metabolismo , Transdução de Sinais , Proteoma/metabolismo , Controle de Qualidade
5.
Hematol Oncol Clin North Am ; 38(4): 743-753, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38724285

RESUMO

Precursor diseases of multiple myeloma (MM) are monoclonal gammopathy of uncertain significance and smoldering MM. While it is well known that a percentage of those affected by these conditions will progress to MM, it is difficult to predict who will progress and when, and guidelines for screening for these conditions are lacking. Moreover, there are various models for risk stratification, though there are ongoing efforts to improve these models in order to predict who may benefit from treatment. Finally, there are various clinical trials, both past and ongoing, expanding the scope of possible treatment options for precursor diseases.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/terapia , Mieloma Múltiplo Latente/diagnóstico , Mieloma Múltiplo Latente/terapia , Detecção Precoce de Câncer/métodos , Progressão da Doença , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Diagnóstico Precoce
6.
JCI Insight ; 9(10)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713510

RESUMO

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 human IL-6-transgenic (hIL-6-transgenic) NSG (NSG+hIL6) mice reliably support the engraftment of malignant and premalignant human plasma cells, including from patients diagnosed with monoclonal gammopathy of undetermined significance, pre- and postrelapse myeloma, plasma cell leukemia, and amyloid light chain amyloidosis. Consistent with human disease, NSG+hIL6 mice engrafted with patient-derived myeloma cells developed serum M spikes, and a majority developed anemia, hypercalcemia, and/or bone lesions. Single-cell RNA sequencing showed nonmalignant and malignant cell engraftment, the latter expressing a wide array of mRNAs associated with myeloma cell survival and proliferation. Myeloma-engrafted mice given CAR T cells targeting plasma cells or bortezomib experienced reduced tumor burden. Our results establish NSG+hIL6 mice as an effective patient-derived xenograft model for study and preclinical drug development of multiple myeloma and related plasma cell disorders.


Assuntos
Modelos Animais de Doenças , Interleucina-6 , Mieloma Múltiplo , Animais , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Humanos , Camundongos , Interleucina-6/metabolismo , Camundongos Transgênicos , Bortezomib/farmacologia , Bortezomib/uso terapêutico , Masculino , Feminino , Plasmócitos/imunologia , Gamopatia Monoclonal de Significância Indeterminada/imunologia , Gamopatia Monoclonal de Significância Indeterminada/patologia
7.
Hematology ; 29(1): 2352686, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38819332

RESUMO

BACKGROUND: Data on the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in China are very limited. Our aim was to determine the prevalence and clinical characteristics of MGUS in a large Chinese population. METHODS: This study included 49,220 healthy people who received serum immunofixation electrophoresis (sIFE) and serum protein electrophoresis (SPE) tests. Serum free light chain ratio, immunoglobulin quantification, and other clinically correlates of MGUS were performed for all patients with M-protein. RESULTS: A total of 576 MGUS patients were identified by sIFE, with a median age of 58 years and an overall prevalence of 1.17% (95% CI, 1.08-1.27). Among those aged 50 years and older, the prevalence of MGUS was 2.26% (95% CI, 2.04-2.50). The prevalence of MGUS was significantly higher in males than in females (P < 0.05). The median concentration of M-protein was 3.1 g/L, ranging from 0.5 g/L to 25.1 g/L. The M-protein type was IgG in 55.4% of MGUS patients, followed by IgA (31.1%), IgM (9.5%), IgD (0.5%), biclonal (2.3%), and light chain (1.2%). Abnormalities in SPE, FLC ratios, and immunoglobulin levels were observed in 78.3%, 31.1%, and 38.4% of MGUS patients, respectively. CONCLUSIONS: The prevalence of MGUS is substantially lower in southern China than in whites and blacks.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Humanos , Masculino , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Gamopatia Monoclonal de Significância Indeterminada/sangue , China/epidemiologia , Feminino , Pessoa de Meia-Idade , Prevalência , Idoso , Adulto , Idoso de 80 Anos ou mais , Adolescente , Adulto Jovem
8.
Ann Intern Med ; 177(6): 711-718, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38768457

RESUMO

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. In previous registry-based, retrospective studies, autoimmune diseases have been associated with MGUS. However, these studies were not based on a screened population and are therefore prone to ascertainment bias. OBJECTIVE: To examine whether MGUS is associated with autoimmune diseases. DESIGN: A cross-sectional study within iStopMM (Iceland Screens, Treats, or Prevents MM), a prospective, population-based screening study of MGUS. SETTING: Icelandic population of adults aged 40 years or older. PATIENTS: 75 422 persons screened for MGUS. MEASUREMENTS: Poisson regression for prevalence ratios (PRs) of MGUS among persons with or without an autoimmune disease, adjusted for age and sex. RESULTS: A total of 10 818 participants had an autoimmune disorder, of whom 599 had MGUS (61 with a prior clinical diagnosis and 538 diagnosed at study screening or evaluation). A diagnosis of an autoimmune disease was not associated with MGUS (PR, 1.05 [95% CI, 0.97 to 1.15]). However, autoimmune disease diagnoses were associated with a prior clinical diagnosis of MGUS (PR, 2.11 [CI, 1.64 to 2.70]). LIMITATION: Registry data were used to gather information on autoimmune diseases, and the homogeneity of the Icelandic population may limit the generalizability of these results. CONCLUSION: The study did not find an association between autoimmune disease and MGUS in a systematically screened population. Previous studies not done in systematically screened populations have likely been subject to ascertainment bias. The findings indicate that recommendations to routinely screen patients with autoimmune disease for MGUS may not be warranted. PRIMARY FUNDING SOURCE: The International Myeloma Foundation and the European Research Council.


Assuntos
Doenças Autoimunes , Programas de Rastreamento , Gamopatia Monoclonal de Significância Indeterminada , Humanos , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Masculino , Feminino , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/complicações , Islândia/epidemiologia , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Adulto , Programas de Rastreamento/métodos , Prevalência , Estudos Prospectivos
9.
Leuk Lymphoma ; 65(7): 989-996, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38581379

RESUMO

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a clonal plasma cell disorder that is considered preneoplastic, asymptomatic, and only requiring observation. However, MGUS may result in cutaneous complications, which are poorly understood, causing treatment delays and patient suffering. We present 30 patients with cutaneous findings associated with MGUS, characterizing clinical presentations, isoforms, treatments, and outcomes. These included: MGUS-associated 'rashes' (pruritic eczematous rashes), reactive and mucin-depositional conditions (pyoderma gangrenosum, scleromyxedema), M-protein-related deposition disorders (POEMS syndrome, Waldenstrom macroglobulinemia), and cutaneous lymphomas. Twelve of 30 (40%) patients received multiple myeloma drugs (MMDs). Eleven (92%) patients improved, and those not receiving MMDs rarely improved, suggesting that MMDs have efficacy for cutaneous manifestations of MGUS. Therefore, trialing MMDs may be warranted for patients with MGUS not responding to other therapies. Moreover, evaluation for monoclonal gammopathy in elderly patients with intractable pruritus or other chronic skin conditions that are non-responsive to skin-directed therapies should be considered.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Dermatopatias , Humanos , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/patologia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Dermatopatias/etiologia , Dermatopatias/diagnóstico , Dermatopatias/patologia , Idoso de 80 Anos ou mais , Adulto , Pele/patologia
10.
Sci Rep ; 14(1): 7667, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561447

RESUMO

Renal involvement is common in monoclonal gammopathy (MG); however, the same patient may have both MG and non-paraprotein-associated renal damage. Accordingly, distinguishing the cause of renal damage is necessary because of the different clinical characteristics and associated treatments. In this multicenter retrospective cohort study, we described the clinicopathological characteristics and prognosis of 703 patients with MG and renal damage in central China. Patients were classified as having MG of renal significance (MGRS), MG of undetermined significance (MGUS), or hematological malignancy. 260 (36.98%), 259 (36.84%), and 184 (26.17%) had MGRS, MGUS, and hematological malignancies, respectively. Amyloidosis was the leading pattern of MGRS (74.23%), followed by thrombotic microangiopathy (8.85%) and monoclonal immunoglobulin deposition disease (8.46%). Membranous nephropathy was the leading diagnosis of MGUS (39.38%). Renal pathological findings of patients with hematological malignancies included paraprotein-associated lesions (84.78%) and non-paraprotein-associated lesions (15.22%). The presence of nephrotic syndrome and an abnormal free light chain (FLC) ratio were independently associated with MGRS. The overall survival was better in patients with MGUS than in those with MGRS or hematological malignancies.


Assuntos
Neoplasias Hematológicas , Nefropatias , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Humanos , Estudos Retrospectivos , Nefropatias/diagnóstico , Nefropatias/etiologia , Nefropatias/patologia , Paraproteinemias/complicações , Paraproteinemias/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Prognóstico , Neoplasias Hematológicas/complicações
11.
Ann Intern Med ; 177(4): 449-457, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38560901

RESUMO

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management. OBJECTIVE: To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model. DESIGN: iStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma), a prospective population-based screening study of MGUS. (ClinicalTrials.gov: NCT03327597). SETTING: Icelandic population of adults aged 40 years or older. PATIENTS: 1043 persons with IgG, IgA, light-chain, and biclonal MGUS detected by screening and an interpretable bone marrow sample. MEASUREMENTS: Monoclonal gammopathy of undetermined significance isotype; monoclonal protein concentration; free light-chain ratio; and total IgG, IgM, and IgA concentrations were used as predictors. Bone marrow plasma cells were categorized as 0% to 4%, 5% to 9%, 10% to 14%, or 15% or greater. RESULTS: The c-statistic for SMM or worse was 0.85 (95% CI, 0.82 to 0.88), and calibration was excellent (intercept, -0.07; slope, 0.95). At a threshold of 10% predicted risk for SMM or worse, sensitivity was 86%, specificity was 67%, positive predictive value was 32%, and negative predictive value was 96%. Compared with the Mayo Clinic model, the net benefit for the decision to refer for sampling was between 0.13 and 0.30 higher over a range of plausible low-risk thresholds. LIMITATION: The prediction model will require external validation. CONCLUSION: This accurate prediction model for SMM or worse was developed in a population-based cohort of persons with presumed MGUS and may be used to defer bone marrow sampling and referral to hematology. PRIMARY FUNDING SOURCE: International Myeloma Foundation and the European Research Council.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Paraproteinemias , Mieloma Múltiplo Latente , Adulto , Humanos , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Medula Óssea , Estudos de Coortes , Estudos Prospectivos , Imunoglobulina A , Imunoglobulina G , Progressão da Doença
12.
BMJ Case Rep ; 17(4)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38670567

RESUMO

We report a man in his 70s who presented with discrepant serum creatinine concentrations in different hospitals at the same time. Further examinations of these discrepancies revealed turbidity of the serum sample and, thus, a reagent reaction and false hypercreatinine caused by paraprotein interference were suspected. Serum protein electrophoresis revealed a small amount of monoclonal γ globulin (2.9 g/L), which may have been involved in paraprotein interference. Monoclonal λ-type IgG was detected in the serum, resulting in a diagnosis of monoclonal gammopathy of undetermined significance. Previous studies indicated paraprotein interference in serum containing monoclonal IgM or a large amount of IgG (> 25 g/L). Although this case of paraprotein interference induced by a small amount of IgG is rare, a discrepancy in creatinine results may be an indicator leading to the diagnosis of plasma cell proliferative diseases.


Assuntos
Creatinina , Gamopatia Monoclonal de Significância Indeterminada , Paraproteínas , Humanos , Masculino , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/sangue , Creatinina/sangue , Paraproteínas/análise , Idoso , Imunoglobulina G/sangue , Eletroforese das Proteínas Sanguíneas
13.
Aging (Albany NY) ; 16(5): 4169-4190, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38431306

RESUMO

BACKGROUND: Multiple myeloma (MM) is an incurable malignant plasma cell disease. We explored the role of RAB22A in exosome secretion, epithelial-mesenchymal transition (EMT) and immune regulation. METHODS: We obtained MM samples from Gene Expression Omnibus (GEO) data sets. We downloaded the "IOBR" package, and used the "PCA" and "ssGSEA" algorithms to calculate the EMT scores and exosome scores. The "CIBERSORT" package was used to analyze the infiltration of immune cells. We extracted the exosomes of mesenchymal stem cell (MSC) to verify the biological function of RAB22A. RESULTS: The expression level of RAB22A in smoldering multiple myeloma (SMM) and MM patients was significantly higher than that in normal people and monoclonal gammopathy of undetermined significance (MGUS) patients, and the expression level of RAB22A in relapse MM patients was significantly higher than that in newly diagnosed patients. The EMT scores and exosome scores of high RAB22A group were significantly higher than those of low RAB22A group, and the exosome scores of MSC in recurrent patients were significantly higher than those of newly diagnosed patients. In addition, the infiltration levels of monocyte, NK cells resting, eosinophils, T cells regulatory and T cells CD4 memory activated were positively correlated with RAB22A. After down-regulating the expression of RAB22A in MM-MSC, the secretion of exosomes decreased. Compared with the exosomes of MSC in si-RAB22A group, the exosomes in control group significantly promoted the proliferation of MM. CONCLUSIONS: RAB22A is a potential therapeutic target to improve the prognosis of MM, which is closely related to exosome secretion, EMT and immune cell infiltration.


Assuntos
Exossomos , Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/metabolismo , Exossomos/metabolismo , Prognóstico , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/genética , Gamopatia Monoclonal de Significância Indeterminada/metabolismo , Doença Crônica , Recidiva , Progressão da Doença , Proteínas rab de Ligação ao GTP/genética
15.
Br J Haematol ; 204(4): 1141-1142, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38429858

RESUMO

In this issue, the British Society for Haematology presents guidelines for the diagnosis and management of patients with smouldering multiple myeloma (SMM). The authors provide a practical, evidence-based approach to managing these patients. Key questions remain yet unsolved. Commentary on: Hughes et al. Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper. Br J Haematol 2024;204:1193-1206.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Mieloma Múltiplo Latente , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Mieloma Múltiplo Latente/terapia , Progressão da Doença
16.
Integr Cancer Ther ; 23: 15347354241242099, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529782

RESUMO

Patients with intermediate-high risk MGUS are not offered therapeutic options to date and standard of care remains observation with re-evaluations of the patient every 3 to 6 months. Given the persistent risk of progression as well as potential complications experienced by some, and anxiety experienced by most patients, early intervention with non-toxic curcumin, aimed at potentially slowing down or stopping disease progression might be therapeutic. We present here an intermediate-high risk MGUS patient who has been taking curcumin for 16 years and has shown a decrease in disease markers and an increase in uninvolved immunoglobulins, adding to the body of evidence of benefit of curcumin to MGUS patients.


Assuntos
Curcumina , Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Humanos , Gamopatia Monoclonal de Significância Indeterminada/tratamento farmacológico , Gamopatia Monoclonal de Significância Indeterminada/complicações , Curcumina/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Progressão da Doença
17.
Eur J Haematol ; 113(1): 72-81, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38553844

RESUMO

OBJECTIVES: Bacterial infections are common and a major cause of morbidity and mortality in multiple myeloma (MM). We have investigated the function of polymorphonuclear leukocyte (PMN), the immune system's first line of defense against bacteria, in peripheral blood (PB) and bone marrow (BM) samples from patients with newly diagnosed MM (NDMM), smoldering MM (SMM), monoclonal gammopathy of undetermined significance (MGUS) and healthy controls. METHODS: Phagocytosis and oxidative burst in PMN cells from patients and healthy donors were investigated using PhagoTest and PhagoBurst assay. RESULTS: PMN from NDMM, SMM, and MGUS patients had reduced phagocytosis and oxidative burst ability compared with healthy controls. The dysfunction was most prominent in BM samples from MM, SMM, and MGUS patients. Importantly the reduced phagocytosis in MM patients was restored in patients on lenalidomide therapy. Consistently the ability of Escherichia coli stimulated oxidative burst in BM was reduced for the MM, SMM, and MGUS cohort in contrast to the healthy controls and the patients on lenalidomide treatment. CONCLUSION: Our results show that MM patients have neutrophil dysfunction that could contribute to susceptibility for bacterial infections and that lenalidomide therapy was associated with restored PMN function.


Assuntos
Lenalidomida , Mieloma Múltiplo , Neutrófilos , Fagocitose , Explosão Respiratória , Humanos , Lenalidomida/uso terapêutico , Neutrófilos/imunologia , Neutrófilos/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/diagnóstico , Fagocitose/efeitos dos fármacos , Explosão Respiratória/efeitos dos fármacos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos de Casos e Controles , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/tratamento farmacológico , Adulto , Idoso de 80 Anos ou mais , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Talidomida/farmacologia , Medula Óssea/patologia , Medula Óssea/metabolismo
18.
Int J Mol Sci ; 25(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38474117

RESUMO

Gaucher disease (GD, OMIM 230800) is one of the most common lysosomal disorders, being caused by the deficient activity of the enzyme acid ß-glucocerebrosidase (Gcase). Three clinical forms of Gaucher's disease (GD) are classified based on neurological involvement. Type 1 (GD1) is non-neuronopathic, while types 2 (GD2) and 3 (GD3) are neuronopathic forms. Gcase catalyzes the conversion of glucosylceramide (GlcCer) into ceramide and glucose. As GlcCer accumulates in lysosomal macrophages, it undergoes deacylation to become glycosylsphingosine (lyso-Gb1), which has shown to be a useful and reliable biomarker for the diagnosis and monitoring of treated and untreated patients with GD. Multiple myeloma (MM) is one of the leading causes of cancer-related death among patients with GD and monoclonal gammopathy of undetermined significance (MGUS) is a non-neoplastic condition that can be a telltale sign of a B clonal proliferation caused by the chronic activation of B cells. This study aimed to quantify Lyso-Gb1 levels in dried blood spots (DBS) and cerebrospinal fluid (CSF) as biomarkers for Gaucher disease (GD) and discuss the association of this biomarker with other clinical parameters. This is a mixed-methods study incorporating both cross-sectional and longitudinal elements within a cohort design with a convenience-sampling strategy. Data collection took place from January 2012 to March 2023. Lyso-Gb1 extraction from DBS involved the use of a methanol-acetonitrile-water mixture, followed by incubation and centrifugation. Analysis was performed using UPLC-MS/MS with MassLynx software version 4.2 and the control group for the DBS measurements included general newborns. CSF Lyso-Gb1 was extracted using ethyl acetate, analyzed by UPLC-MS/MS with a calibration curve, and expressed in pmol/L. Lysosomal activity in CSF was assessed by measuring chitotriosidase (Cht), and other lysosomal enzyme activities were assessed as previously described in the literature. Patients with metachromatic leukodystrophy (MLD) were used as controls. Thirty-two treated patients (twenty-nine GD1 and three GD3, all on ERT except for one GD type on SRT with eliglustat) and three untreated patients (one GD1, one GD2, and one GD3) were included. When analyzing only the treated GD1 group, a significant correlation was found between lyso-Gb1 and age (rho = -0.447, p = 0.001), ChT, and IgG levels (rho = 0.73, p < 0.001; and rho = 0.36, p = 0.03, respectively). Five GD1 patients (three females, mean age 40 years) also had their CSF collected and analyzed. The average measurement of lyso-Gb1 in CSF was 94 pmol/L (range: 57.1-157.9 pmol/L) versus <6.2 pmol/L in the control group (MLD). This is the first time, to the best of our knowledge, that lyso-Gb1 has been associated with IgG levels. While this finding reflects a risk for MGUS or MM and not only chronic plasma B-cell activation, it still requires further studies. Moreover, the analysis of CSF lyso-Gb1 levels in GD1 patients was demonstrated to be significantly higher than the control group. This raises the hypothesis that CSF lyso-Gb1 may serve as a valuable indicator for neurological involvement in GD, providing insights into the potential implications for neurological manifestations in GD, including GD1. The correlation between lyso-Gb1 and ChT levels in treated GD1 patients further underscores the interconnectedness of lysosomal markers and their relevance in monitoring.


Assuntos
Doença de Gaucher , Gamopatia Monoclonal de Significância Indeterminada , Psicosina , Adulto , Feminino , Humanos , Recém-Nascido , Biomarcadores , Brasil , Cromatografia Líquida , Estudos Transversais , Doença de Gaucher/diagnóstico , Imunoglobulina G/sangue , Psicosina/análogos & derivados , Espectrometria de Massas em Tandem
19.
In Vivo ; 38(2): 954-957, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38418115

RESUMO

BACKGROUND/AIM: The presence of a monoclonal gammopathy of undetermined significance (MGUS) even in small amounts may trigger tissue damage through immunological or other mechanisms, irrespective of the potential for malignant transformation. The aim of the study was to present a case of monoclonal gammopathy of clinical significance with ocular manifestations and discuss relevant literature. CASE REPORT: In our case, a patient presented with vision disturbances that was eventually attributed to the underlying IgM MGUS after extensive workup to exclude other potential etiologies. The patient showed a clinical response with the fixed-duration DRC (dexamethasone, rituximab, cyclophosphamide) regimen that persisted for at least 1.5 years. Herein, we present, in detail, the patient management and discuss the underlying pathophysiology of this rare entity with few available published data in this field. CONCLUSION: A high level of clinical suspicion is necessary in order to detect the association between MGUS and a clinical sign or symptom that cannot be attributed elsewhere.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Doenças Retinianas , Humanos , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Ciclofosfamida , Imunoglobulina M , Transformação Celular Neoplásica
20.
Clin Biochem ; 126: 110730, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387751

RESUMO

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. When concomitantly one Ig presented a value above and one below its reference interval, the LIS automatically registered a serum protein electrophoresis (SPEP). When a monoclonal peak in SPEP, immunofixation electrophoresis (IFE) for the typification of monoclonal bands (MB) was performed. If MB were present, a comment in the report explained the intervention. The number of additionally registered Ig, SPEP, IFE, and new diagnosis of MM were counted. The number of days elapsed from the report of elevated STP result to the final MM diagnosis was also counted as median and interquartile range (IQR), and compared to a pre intervention period. RESULTS: 2071 cases of hyperproteinemia were identified, and had 91 a monoclonal peak, confirmed by IFE. In 35 patients it was a new finding, and 9 were diagnosed with MM, 3 Waldestrom macroglobulinemia, 2 lymphoplasmacytic lymphoma and 21 monoclonal gammopathy of undetermined significance. The number of days elapsed from hyperproteinemia to diagnosis was lower in the intervention period (21.5 vs 119.4) (P < 0.01). As our results show, in addition to shortening the time to diagnosis, an increased rate of detection of plasma cell disorders was observed when using our algorithm. CONCLUSIONS: The above laboratory interventions agreed with clinicians, making use of laboratory technology resulted in early identification of MM.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Paraproteinemias , Humanos , Mieloma Múltiplo/diagnóstico , Paraproteinemias/diagnóstico , Reflexo , Atenção Primária à Saúde
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