Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical significance of the BJ-protein is quite variable: from an asymptomatic course of the light chain proteinuria for a long period of time to specific tissue deposits with serious organ damages and dysfunction. On the basis of literature data a classification of the light chain diseases is proposed: 1. Essential (bening) BJ-proteinuria; 2. Smoldering BJ-myeloma; 3. Light chain disease--BJ myeloma; 4. Light (and heavy) chain deposition disease: LC granular thick deposits mostly k type on electron microscopy, belonging to the constant region of the polypeptide chain and actively reacting with antiserums, not possessing tincturial properties; 5. LC cast nephropathy--LC coprecipitates in the tubular system; 6. LC crystaline deposition disease--specific crystaloid structures (in the Fanconi syndrome and experimental nephropathies); 7. AL-amyloidosis: LC precursor mostly lambda type from the variable region with specific fibrilar structure and typical tincturial properties. The suggested classification would resolve the diagnostic difficulties and determine the correct therapeutic management.
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PMID:[Light chain diseases--pathogenetic forms, diagnostic criteria. A suggestion for classification]. 1122 63

A 45 year old man with IgA-Kappa myeloma had adult Fanconi Syndrome. Examination of renal biopsy revealed lesions in proximal tubules without glomerular lesions and without intratubular casts. By electron microscopy cytoplasmic crystalline inclusions were observed in renal proximal tubular epithelium. Increased plasma cells (28%) in bone marrow aspiration also contained crystalline inclusions. The treatment of myeloma produced partial remission of proliferative disease and Fanconi syndrome. We discuss the pathogenesis of Fanconi syndrome induced by light chains as well as the composition of crystalline deposits and the effects of treatment on Fanconi Syndrome.
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PMID:[Intracytoplasmic crystals and Fanconi syndrome in a patient with IgA kappa myeloma]. 1146 57

A 45-year-old male was admitted because of chest pain, lumbago, and bilateral ankle pain. Examination disclosed hypophosphatemic osteomalacia, acquired Fanconi syndrome, and abnormalities in distal nephron such as distal renal tubular acidosis and renal diabetes insipidus. Further exploration revealed IgA kappa multiple myeloma excreting urinary Bence Jones protein (kappa-light chain). Renal biopsy revealed thick basement membranes and elec-tron-dense crystals in proximal tubular epithelial cells. Immunofluorescent studies revealed deposition of kappa-light chain in renal tubular epithelial cells that caused the renal tubular damage. Although the osteomalacia was relieved by medical treatment, the urinary Bence Jones protein and the renal tubular defects were not improved by the chemotherapy for the myeloma. The patient died of exacerbation of multiple myeloma at 50 years of age.
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PMID:IgA-kappa type multiple myeloma affecting proximal and distal renal tubules. 1157 59

Several plasma cells morphological changes have been described in monoclonal gammopathies, including intracytoplasmic crystals. We report one case of indolent kappa-chain multiple myeloma with renal insufficiency, featuring plasma cells with Auer-rod-like intracytoplasmic inclusions. The relationship between such aberrations and those found in multiple-myeloma-associated adult Fanconi syndrome is discussed. The significance of intracellular storage and crystallisation of immunoglobulin within plasma cells remains partially unknown.
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PMID:Is there any significance for intracellular crystals in plasma cells from patients with monoclonal gammopathies? 1172

Calcium and phosphate metabolism abnormalities are frequent in myeloma patients and the role of renal lesions in such ionic perturbations may have been overlooked. The authors herein report the complete primary structure of a Bence Jones Vkappal light chain responsible for myeloma-associated proximal tubulopathy with increased phosphaturia. Plasma and serum biochemical evaluations indicated a proximal tubular dysfunction mainly manifested as tubular acidosis and phosphate loss. The study of a kidney biopsy showed interstitial and tubular lesions with numerous myeloma casts and peculiar features of the proximal tubular cells, which carried numerous phagolysosomal inclusions with occasional crystalline periodic striation. The nephrotoxic light chain primary structure was deduced from the bone marrow monoclonal plasma cells RNA. The kappal sequence was highly homologous to kappa chains previously characterized in patients with Fanconi syndrome. It was related to the Vkappal subgroup and was composed of a variable segment encoded by the O8/O18 germline gene rearranged to Jkappa4. The primary sequence presented unusual features restricted to the variable region, including substitutions of residues 28 and 31 in the complementary determining region 1 (CDR1) by amino acids of different charge. An unusual conformation of the kappal domain, likely resulting from somatic hypermutation, could alter the catabolism of the protein after its internalization and result in the tubular cell dysfunction. Comparison with Fanconi syndrome studies suggests that Vkappal Bence Jones proteins may damage proximal tubular cells to an extent varying according to light chain (LC) sequence and structure, either leading to crystal formation and Fanconi syndrome or inducing partial inhibition of proximal tubule function.
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PMID:A monoclonal V kappa l light chain responsible for incomplete proximal tubulopathy. 1255 16

As a result of studying the urine proteins of 223 individuals by starch gel electrophoresis, a new urine protein fraction has been recognized. On starch gel electrophoresis at alkaline pH the new fraction moves to a position appreciably nearer the cathode than the slowest-moving gamma-globulin in normal serum. A small amount of this post-gamma protein was found in the urine of 46 patients with clinical proteinuria, including 19 with the Fanconi syndrome and nine with multiple myeloma. The nature, origin, and clinical significance of post-gamma protein is discussed.
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PMID:The occurrence of post-gamma protein in urine: a new protein abnormality. 1368 27

Cancer cell adhesion confers a transient, de novo drug-resistant phenotype referred to as cell adhesion-mediated drug resistance (CAM-DR). In this report, we extend the CAM-DR phenotype to primary specimens from patients with myeloma, providing further evidence that CAM-DR is a viable clinical form of drug resistance. To examine mechanisms of cellular resistance to melphalan, we compared genotypic and phenotypic profiles of acquired and de novo melphalan resistance in an isogenic human myeloma cell line. Acquired melphalan resistance (8226/LR5) was associated with decreased drug-induced DNA damage and a complex gene expression profile showing that genes involved in the Fanconi anemia DNA repair pathway are increased in the LR5 cells compared with drug-sensitive or adherent cells. In contrast, cells adhered to fibronectin accumulate similar amounts of DNA damage compared with drug-sensitive cells but are protected from melphalan-induced mitochondrial perturbations and caspase activation. Levels of the proapoptotic protein Bim were significantly reduced in adherent cells. Gene expression changes associated with de novo resistance were significantly less complex compared with acquired resistance, but a significant overlap in gene expression was noted involving cholesterol synthesis. We propose that myeloma cell adhesion promotes a form of de novo drug resistance by protecting cells from melphalan-induced cytotoxic damage and that this transient protection allows cells to acquire a more permanent and complex drug resistance phenotype associated with a reduction in drug induced DNA damage.
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PMID:Genotypic and phenotypic comparisons of de novo and acquired melphalan resistance in an isogenic multiple myeloma cell line model. 1463 19

Dysproteinemia is a clinical state characterized by abnormal, often excessive, synthesis of immunoglobulin (Ig) molecules or subunits. Dysproteinemia results from clonal proliferation of plasma cells or B lymphocytes. The abnormal circulating Ig molecules or subunits (most commonly free light chains) reach the glomerulus via the systemic circulation and are associated with the development of a variety of pathologic lesions within the kidney. Free light chain molecules may pass through the glomerular basement membrane and form casts within distal tubular lumina (myeloma cast nephropathy) or form crystals within the cytoplasm of proximal tubules (light chain Fanconi syndrome). Alternatively, Ig molecules or subunits may form paraprotein tissue deposits and produce an array of pathologic lesions, most commonly amyloidosis and monoclonal Ig deposition disease. The pattern of renal parenchymal disease is determined by the unique properties of the Ig molecule or subunit. Each of the patterns of renal disease is in turn associated with unique, but frequently overlapping, clinical features and outcomes. This review emphasizes the pathologic, clinical, and prognostic differences among the patterns of renal parenchymal disease related to dysproteinemia.
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PMID:Dysproteinemia and the kidney. 1467 40

We have reviewed the world's literature that addresses familial leukemia, lymphoma, and myeloma. We have catalogued the phenotypic abnormalities associated with an increased risk of developing a hematological malignancy. These syndromes, such as Fanconi anemia or familial platelet syndrome, have been well characterized and in many cases the gene responsible for the predisposition has been defined. We have focused, however, on reports of a familial incidence of hematological malignancy in which no prior predisposing syndrome was reported. In this circumstance, so-called pure familial leukemia, lymphoma, or myeloma, the intergenerational incidence of disease occurred in ostensibly healthy persons. These families have been grouped into sets in which (a) anticipation, (b) immune abnormalities, (c) linkage to HLA phenotypes, (d) linkage to chromosome abnormalities, or (e) gene abnormalities have been reported. They have also been grouped by type of leukemia. Purely descriptive reports, not accompanied by some information on pathogenesis, have not been included. They are catalogued in some of the references cited in this paper. Anticipation is a prominent feature of familial leukemia, lymphoma, and myeloma, supporting the concept of germline transmission of a susceptibility gene. Although linkage to an HLA phenotype occurs in some families, no consistent intrafamilial pattern has emerged. Deletion of chromosome 7 is associated with familial acute myelogenous leukemia, but no other recurring localization has been established. Although putative susceptibility genes have been identified in some families, the likelihood is that the mode of inheritance is different in different families and different genes are involved even within a specific Mendelian pattern. Although as yet not reported, the frequency of familial CLL and the intensity of its study indicates that the gene or genes involved in that familial disorder(s) should be identified conclusively soon if sufficient families for study can be assembled through international cooperation.
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PMID:Familial (inherited) leukemia, lymphoma, and myeloma: an overview. 1475 42

Adult-acquired Fanconi syndrome (FS) is a rare complication of monoclonal gammopathy. We retrospectively reviewed 32 patients diagnosed with adult-acquired FS between April 1968 and June 2002 at Mayo Clinic (Rochester, MN). At diagnosis, most patients had monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM), with a median creatinine level of 176.8 microM (2.0 mg/dL; range, 79.56-327.08 microM [0.9-3.7 mg/dL]) and evidence of osteomalacia. During the average 65 months (range, 2-238 months) of follow-up, 5 patients developed end-stage renal disease (ESRD) and only 1 of 14 patients with MGUS transformed to multiple myeloma (MM). Also, 14 deaths occurred, with only 1 from ESRD but 4 from alkylator-related leukemia or myelodysplastic syndrome. Chemotherapy offered little benefit on renal functions of MGUS or SMM patients. In conclusion, FS associated with monoclonal gammopathy does not appear to confer an additional risk of subsequent evolution to MM. ESRD occurs late in the disease process.
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PMID:Acquired Fanconi syndrome is an indolent disorder in the absence of overt multiple myeloma. 1501 Mar 72


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