Database : MEDLINE
Search on : Monoclonal and Gammopathy and of and Undetermined and Significance [Words]
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[PMID]: 28456791
[Au] Autor:Dondero A; Casu B; Bellora F; Vacca A; De Luisi A; Frassanito MA; Cantoni C; Gaggero S; Olive D; Moretta A; Bottino C; Castriconi R
[Ad] Address:Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy.
[Ti] Title:NK cells and multiple myeloma-associated endothelial cells: molecular interactions and influence of IL-27.
[So] Source:Oncotarget;8(21):35088-35102, 2017 May 23.
[Is] ISSN:1949-2553
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Angiogenesis represents a hallmark of tumor progression in Multiple Myeloma (MM), a still incurable malignancy. Here we analyzed the activity of cytokine-stimulated NK cells against tumor-associated endothelial cells isolated from bone marrow aspirates of MM patients with active disease (MMECs). We show that NK cells activated with optimal doses of IL-15 killed MMECs thanks to the concerted action of multiple activating receptors. In particular, according to the high expression of PVR and Nectin-2 on MMECs, DNAM-1 actively participated in target recognition. Interestingly, in MMECs the surface density of PVR was significantly higher than that detected in endothelium from patients with MM in complete remission or with monoclonal gammopathy of undetermined significance (MGUS). Importantly, IL-27, which unlike IL-15 does not display pro-angiogenic properties, maintained or increased the NK cell functions induced by suboptimal concentrations of IL-15. NK cell properties included killing of MMECs, IFN-γ production as well as a peculiar increase of NKp46 expression on NK cell surface. Finally, IL-27 showed a striking capability of up-regulating the expression of PD-L2 and HLA-I on tumor endothelium, whereas it did not modify that of PD-L1 and HLA-II.Our results suggest that cytokine-activated endogenous or adoptively transferred NK cells might support conventional therapies improving the outcome of MM patients.
[Mh] MeSH terms primary: Endothelial Cells/drug effects
Interleukins/metabolism
Killer Cells, Natural/drug effects
Multiple Myeloma/immunology
[Mh] MeSH terms secundary: Aged
Endothelial Cells/cytology
Endothelial Cells/metabolism
Female
Humans
Interleukin-15/pharmacology
Killer Cells, Natural/cytology
Killer Cells, Natural/metabolism
Male
Middle Aged
Multiple Myeloma/metabolism
Neovascularization, Pathologic
Receptors, Virus/metabolism
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (IL27 protein, human); 0 (Interleukin-15); 0 (Interleukins); 0 (Receptors, Virus); 0 (poliovirus receptor)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:170501
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.17070

  2 / 2173 MEDLINE  
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[PMID]: 29515067
[Au] Autor:Kanamori T; Kusumoto S; Okita K; Hagiwara S; Kato C; Nakashima T; Murakami S; Narita T; Ito A; Ri M; Ishida T; Komatsu H; Matsukawa N; Iida S
[Ad] Address:Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences.
[Ti] Title:[Sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance mimicking POEMS syndrome].
[So] Source:Rinsho Ketsueki;59(2):161-166, 2018.
[Is] ISSN:0485-1439
[Cp] Country of publication:Japan
[La] Language:jpn
[Ab] Abstract:A 40-year-old female presented with a skin rash, hepatosplenomegaly, hypothyroidism, IgG-λ monoclonal gammopathy, slightly elevated serum VEGF levels, and >1-year history of weakness in the posterior cervical muscles. Based on these symptoms and her clinical course, she was suspected of having POEMS syndrome. However, because there was no sign of peripheral neuropathy (PN), the criteria for the diagnosis of POEMS syndrome were not met. Consequently, she continued follow-up and was under close observation as an outpatient. She complained of slowly progressive dyspnea that was identified as type 2 respiratory failure requiring non-invasive positive pressure ventilation. She received systemic chemotherapy, including thalidomide and dexamethasone, as the respiratory failure was predominantly a result of POEMS-associated PN. Although the skin eruptions improved upon treatment, respiratory failure gradually worsened, and she required mechanical ventilation. The patient was suspected of having sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance (SLONM-MGUS), because of resistant to chemotherapy and second opinion suggestion. A thigh muscle biopsy revealed the presence of nemaline rods and led to the definitive diagnosis of SLONM-MGUS. Unfortunately, she was unable to receive autologous stem cell transplantation, and finally died because of progressive respiratory failure. SLONM-MGUS is an extremely rare disease but should be considered as a critical, monoclonal-protein related condition.
[Pt] Publication type:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.11406/rinketsu.59.161

  3 / 2173 MEDLINE  
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[PMID]: 29492600
[Au] Autor:Vander Meeren S; Heyrman B; Renmans W; Bakkus M; Maes B; De Raeve H; Schots R; Jochmans K
[Ad] Address:Department of Clinical Biology, Hematology Division, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium. Sam.vandermeeren@uzbrussel.be.
[Ti] Title:Lymphoma-like monoclonal B cell lymphocytosis in a patient population: biology, natural evolution, and differences from CLL-like clones.
[So] Source:Ann Hematol;, 2018 Feb 28.
[Is] ISSN:1432-0584
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:High-count monoclonal B cell lymphocytosis (MBL) with a chronic lymphocytic leukemia (CLL) phenotype is a well-known entity, featuring 1-4% annual risk of progression towards CLL requiring treatment. Lymphoma-like MBL (L-MBL), on the other hand, remains poorly defined and data regarding outcome are lacking. We retrospectively evaluated 33 L-MBL cases within our hospital population and compared them to 95 subjects with CLL-like MBL (C-MBL). Diagnoses of L-MBL were based on asymptomatic B cell clones with Matutes score < 3, B cells < 5.0 × 10 /µl, and negative computerized tomography scans. We found that median B cell counts were considerably lower compared to C-MBL (0.6 vs 2.3 × 10 /µl) and remained stable over time. Based on immunophenotyping and immunogenetic profiling, most L-MBL clones did not correspond to known lymphoma entities. A strikingly high occurrence of paraproteinemia (48%), hypogammaglobulinemia (45%), and biclonality (21%) was seen; these incidences being significantly higher than in C-MBL (17, 21, and 5%, respectively). Unrelated monoclonal gammopathy of undetermined significance was a frequent feature, as the light chain type of 5/12 paraproteins detected was different from the clonal surface immunoglobulin. After 46-month median follow-up, 2/24 patients (8%) had progressed towards indolent lymphoma requiring no treatment. In contrast, 41% of C-MBL cases evolved to CLL and 17% required treatment. We conclude that clinical L-MBL is characterized by pronounced immune dysregulation and very slow or absent progression, clearly separating it from its CLL-like counterpart.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1007/s00277-018-3282-0

  4 / 2173 MEDLINE  
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[PMID]: 29342381
[Au] Autor:Kyle RA; Larson DR; Therneau TM; Dispenzieri A; Kumar S; Cerhan JR; Rajkumar SV
[Ad] Address:From the Divisions of Hematology (R.A.K., A.D., S.K., S.V.R.), Biostatistics (D.R.L., T.M.T.), and Epidemiology (J.R.C.), Mayo Clinic, Rochester, MN.
[Ti] Title:Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance.
[So] Source:N Engl J Med;378(3):241-249, 2018 01 18.
[Is] ISSN:1533-4406
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) occurs in approximately 3% of persons 50 years of age or older. METHODS: We studied 1384 patients who were residing in southeastern Minnesota and in whom MGUS was diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was progression to multiple myeloma or another plasma-cell or lymphoid disorder. RESULTS: During 14,130 person-years of follow-up, MGUS progressed in 147 patients (11%), a rate that was 6.5 times (95% confidence interval [CI], 5.5 to 7.7) as high as the rate in the control population. The risk of progression without accounting for death due to competing causes was 10% at 10 years, 18% at 20 years, 28% at 30 years, 36% at 35 years, and 36% at 40 years. Among patients with IgM MGUS, the presence of two adverse risk factors - namely, an abnormal serum free light-chain ratio (ratio of kappa to lambda free light chains) and a high serum monoclonal protein (M protein) level (≥1.5 g per deciliter) - was associated with a risk of progression at 20 years of 55%, as compared with 41% among patients who had one adverse risk factor and 19% among patients who had neither risk factor. Among patients with non-IgM MGUS, the risk of progression at 20 years was 30% among those who had the two risk factors, 20% among those who had one risk factor, and 7% among those who had neither risk factor. Patients with MGUS had shorter survival than was expected in the control population of Minnesota residents of matched age and sex (median, 8.1 vs. 12.4 years; P<0.001). CONCLUSIONS: Significant differences were noted in the risk of progression between patients with IgM MGUS and those with non-IgM MGUS. Overall survival was shorter among patients with MGUS than was expected in a matched control population. (Funded by the National Cancer Institute.).
[Mh] MeSH terms primary: Disease Progression
Monoclonal Gammopathy of Undetermined Significance/complications
[Mh] MeSH terms secundary: Adult
Aged
Bone Marrow Examination
Female
Follow-Up Studies
Glycoproteins/blood
Humans
Immunoglobulin Light Chains/blood
Immunoglobulin M/blood
Male
Middle Aged
Monoclonal Gammopathy of Undetermined Significance/mortality
Monoclonal Gammopathy of Undetermined Significance/pathology
Multiple Myeloma/etiology
Prognosis
Proportional Hazards Models
Risk Factors
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Name of substance:0 (Glycoproteins); 0 (Immunoglobulin Light Chains); 0 (Immunoglobulin M); 0 (protein M (glycoprotein))
[Em] Entry month:1801
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:180118
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1709974

  5 / 2173 MEDLINE  
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[PMID]: 29506935
[Au] Autor:Cosemans C; Oben B; Arijs I; Daniëls A; Declercq J; Vanhees K; Froyen G; Maes B; Mebis J; Rummens JL
[Ad] Address:Department of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
[Ti] Title:Prognostic Biomarkers in the Progression From MGUS to Multiple Myeloma: A Systematic Review.
[So] Source:Clin Lymphoma Myeloma Leuk;, 2018 Feb 17.
[Is] ISSN:2152-2669
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Multiple myeloma (MM), characterized by malignant plasma cells in the bone marrow, is consistently preceded by asymptomatic premalignant stage monoclonal gammopathy of undetermined significance (MGUS). These MGUS patients have an annual risk of 1% to progress to MM. Clinical, imaging, and genomic (genetic and epigenetic) factors were identified, whose presence increased the risk of progression from MGUS to MM. In this systematic review we summarize the currently identified clinical, imaging, and genomic biomarkers suggested to increase the progression risk or shown to be differentially expressed/present between both cohorts of patients. Despite the wide range of proposed markers, there are still no reliable biomarkers to individually predict which MGUS patient will progress to MM and which will not. Research on biomarkers in the progression from MGUS to MM will give more insight in the unknown pathogenesis of this hematological malignancy. This would improve research by elucidating new pathways and potential therapeutic targets as well as clinical management by closer follow-up and earlier treatment of high-risk MGUS patients.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1803
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[St] Status:Publisher

  6 / 2173 MEDLINE  
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[PMID]: 29311715
[Au] Autor:Ghobrial IM; Detappe A; Anderson KC; Steensma DP
[Ad] Address:Division of Hematological Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02115, USA.
[Ti] Title:The bone-marrow niche in MDS and MGUS: implications for AML and MM.
[So] Source:Nat Rev Clin Oncol;, 2018 Jan 09.
[Is] ISSN:1759-4782
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Several haematological malignancies, including multiple myeloma (MM) and acute myeloid leukaemia (AML), have well-defined precursor states that precede the development of overt cancer. MM is almost always preceded by monoclonal gammopathy of undetermined significance (MGUS), and at least a quarter of all patients with myelodysplastic syndromes (MDS) have disease that evolves into AML. In turn, MDS are frequently anteceded by clonal haematopoiesis of indeterminate potential (CHIP). The acquisition of additional genetic and epigenetic alterations over time clearly influences the increasingly unstable and aggressive behaviour of neoplastic haematopoietic clones; however, perturbations in the bone-marrow microenvironment are increasingly recognized to have key roles in initiating and supporting oncogenesis. In this Review, we focus on the concept that the haematopoietic neoplasia-microenvironment relationship is an intimate rapport between two partners, provide an overview of the evidence supporting a role for the bone-marrow niche in promoting neoplasia, and discuss the potential for niche-specific therapeutic targets.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1801
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[St] Status:Publisher
[do] DOI:10.1038/nrclinonc.2017.197

  7 / 2173 MEDLINE  
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[PMID]: 29183861
[Au] Autor:Horino T; Matsumoto T; Inoue K; Ichii O; Terada Y
[Ad] Address:Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan. Electronic address: horinott@yahoo.co.jp.
[Ti] Title:Bilateral striopallidodentate calcinosis associated with Sjögren's syndrome and IgDλ monoclonal gammopathy of undetermined significance.
[So] Source:Joint Bone Spine;85(2):243-245, 2018 Mar.
[Is] ISSN:1778-7254
[Cp] Country of publication:France
[La] Language:eng
[Ab] Abstract:We presented the first case of bilateral striopallidodentate calcinosis secondary to Sjögren's syndrome. Further consideration should be given to the association between Sjögren's syndrome and bilateral striopallidodentate calcinosis, because Sjögren's syndrome is latent, but more frequent than other autoimmune diseases.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 180303
[Lr] Last revision date:180303
[St] Status:In-Data-Review

  8 / 2173 MEDLINE  
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[PMID]: 29390260
[Au] Autor:Chiang HH; Wieland RS; Rogers TS; Gibson PC; Atweh G; McCormick G
[Ad] Address:University of Vermont College of Medicine.
[Ti] Title:Paraproteinemic keratopathy in monoclonal gammopathy of undetermined significance treated with primary keratoprosthesis: Case report, histopathologic findings, and world literature review.
[So] Source:Medicine (Baltimore);96(50):e8649, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:RATIONALE: We report a case of paraproteinemic keratopathy associated with monoclonal gammopathy of undetermined significance, treated with keratoprosthesis as a primary penetrating procedure. Histopathological findings and a world literature review are presented. PATIENT CONCERNS: A 74 year old female recently diagnosed with monoclonal gammopathy undetermined significance presented with progressive blurry vision bilaterally. DIAGNOSES: Examination revealed corneal opacities consistent with paraproteinemic keratopathy. INTERVENTIONS: Corneal transplantation with the Boston Type I keratoprosthesis was performed on the right and, a year later, on the left. OUTCOMES: Visual outcomes were good. Histopathological staining of host corneal buttons were consistent with monoclonality, and electron microscopy revealed fibrillar extracellular aggregates within intervening normal stroma. LESSONS: Corneal deposits may be the only manifestation of monoclonal gammopathy of undetermined significance in patients who are otherwise systemically asymptomatic. Ophthalmologists who encounter corneal opacities may order the appropriate diagnostic studies to determine the presence of occult systemic disease. Risk of graft failure after penetrating keratoplasty from recurring opacities is high, so keratoprosthesis as a primary penetrating procedure may afford superior long-term outcomes. Host corneal buttons retrieved from penetrating keratoplasty or corneal biopsy may be sent for histopathological examination to confirm the diagnosis.
[Mh] MeSH terms primary: Corneal Diseases/etiology
Corneal Opacity/etiology
Monoclonal Gammopathy of Undetermined Significance/complications
Paraproteinemias/complications
[Mh] MeSH terms secundary: Aged
Corneal Diseases/surgery
Corneal Opacity/surgery
Corneal Transplantation
Female
Humans
Vision Disorders/etiology
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Em] Entry month:1802
[Cu] Class update date: 180301
[Lr] Last revision date:180301
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008649

  9 / 2173 MEDLINE  
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[PMID]: 29269527
[Au] Autor:Go RS; Heien HC; Sangaralingham LR; Habermann EB; Shah ND
[Ad] Address:Division of Hematology Mayo Clinic, Rochester, MN, USA go.ronald@mayo.edu.
[Ti] Title:Risk of progression of monoclonal gammopathy of undetermined significance into lymphoplasmacytic malignancies: determining demographic differences in the USA.
[So] Source:Haematologica;103(3):e123-e125, 2018 Mar.
[Is] ISSN:1592-8721
[Cp] Country of publication:Italy
[La] Language:eng
[Pt] Publication type:LETTER
[Em] Entry month:1712
[Cu] Class update date: 180301
[Lr] Last revision date:180301
[St] Status:In-Data-Review
[do] DOI:10.3324/haematol.2017.179978

  10 / 2173 MEDLINE  
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[PMID]: 29372735
[Au] Autor:Kamande JW; Lindell MAM; Witek MA; Voorhees PM; Soper SA
[Ad] Address:Department of Biomedical Engineering, The University of North Carolina at Chapel Hill, NC 27599, USA.
[Ti] Title:Isolation of circulating plasma cells from blood of patients diagnosed with clonal plasma cell disorders using cell selection microfluidics.
[So] Source:Integr Biol (Camb);10(2):82-91, 2018 Feb 19.
[Is] ISSN:1757-9708
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Blood samples from patients with plasma cell disorders were analysed for the presence of circulating plasma cells (CPCs) using a microfluidic device modified with monoclonal anti-CD138 antibodies. CPCs were immuno-phenotyped using a CD38/CD56/CD45 panel and identified in 78% of patients with monoclonal gammopathy of undetermined significance (MGUS), all patients with smouldering and symptomatic multiple myeloma (MM), and none in the controls. The burden of CPCs was higher in patients with symptomatic MM compared with MGUS and smouldering MM (p < 0.05). FISH analysis revealed the presence of chromosome 13 deletions in CPCs that correlated with bone marrow results. Point mutations in KRAS were identified, including different mutations from sub-clones derived from the same patient. The microfluidic assay represents a highly sensitive method for enumerating CPCs and allows for the cytogenetic and molecular characterization of CPCs.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180220
[Lr] Last revision date:180220
[St] Status:In-Data-Review
[do] DOI:10.1039/c7ib00183e


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