<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Molecular pathogenesis and progression of light chain amyloidosis"^^ . "Light chain amyloidosis is a malignant plasma cell disease characterized by the production and secretion of immunoglobulin light chains, aggregating as amyloid and causing end organ damage, most frequently in heart and kidney.\r\nThe primary aim of this thesis was to assess the molecular background and prognosis of light chain amyloidosis in relation to other malignant plasma cell diseases.\r\nCD138-positive purified malignant plasma cells from patients diagnosed with light chain amyloidosis, monoclonal gammopathy of undetermined significance, asymptomatic and symptomatic multiple myeloma were subjected to interphase fluorescence in situ hybridization (n = 582/306/444/1691), gene expression profiling by DNA microarrays (n = 196/64/271/765), RNA sequencing (n = 124/51/140/515), and whole exome sequencing (light chain amyloidosis n = 113). Clinical and survival data were collected.\r\nFirst, it was shown that for multiple myeloma risk assessment by the gene expression-based HM metascore compared to the current gold-standard (rISS) shows superior delineation of five-year overall survival rate of 98%/68%/25% for low/medium/high risk HM metascore versus 86%/65%/40% for rISS stages I/II/III, respectively.\r\nSecond, it was investigated to what degree prognosis of light chain amyloidosis is determined by free light chain production and amyloid deposition and to what degree by properties of the malignant plasma cells. Till now, early prognosis and risk for patients was seen as defined by amyloid deposition and free light chain secretion, with risk assessment based on serum parameters of cardiac involvement and the difference in free light chains in the serum. Malignant plasma cell characteristics in light chain amyloidosis, represented by chromosomal aberrations, were considered regarding treatment decisions and as defining prognosis rather late during the course of disease.\r\nIn this thesis, it was shown that prognosis of light chain amyloidosis patients is likewise driven by malignant plasma cell factors accessible by gene expression profiling independent of light chain deposition-based factors. This especially holds true for gene expression-based assessment of proliferation (GPI), myeloma-based risk scores (UAMS70, RS), and the de novo for light chain amyloidosis patients generated HDAL score. The hypothesis that the same malignant plasma cell factors determine prognosis in light chain amyloidosis and myeloma was validated by testing the HDAL score’s prognostic significance on two independent groups of asymptomatic and symptomatic multiple myeloma patients. This indicates that the underlying malignant plasma cell\r\ncomponent in both diseases is similar. Thus, early prognosis is also defined by molecular factors of plasma cells.\r\nThird, the similarities and differences regarding malignant plasma cell characteristics were assessed, to determine if light chain amyloidosis is a unique molecular entity and if not, place the underlying malignant plasma cell disease of it in relation to multiple myeloma and its precursor stages to determine a \"molecular age\". \r\nOn a patient level, malignant plasma cells in light chain amyloidosis do not show mayor molecular differences to myeloma. This was shown by dimension reduction, analysis of differentially expressed and mutated genes. A larger variance was detected within samples than between different disease entities. Thus, light chain amyloidosis is not a distinct molecular entity regarding malignant plasma cell characteristics,\r\nand it likewise does not resemble a stage earlier than monoclonal gammopathy of undetermined significance. Differences exist on a population level, i.e. in light chain amyloidosis a large proportion of patients with translocation t(11;14), a small group of highly proliferative samples, and a lower mutational load on average compared to multiple myeloma. Given that all myeloma subgroups are also present in light chain amyloidosis, although at different frequencies, the ability of malignant plasma cells to produce amyloid generating light chains can appear on every myeloma associated molecular background.\r\nIn a nutshell, in respect to gene expression, molecular risk stratification, chromosomal aberrations, copy number alterations, and mutations light chain amyloidosis is a\r\nmalignant plasma cell disease with a median \"molecular age\" between monoclonal gammopathy of undetermined significance and asymptomatic myeloma - atop an \"unlucky\" light chain."^^ . "2022" . . . . . . . "Susanne Monika"^^ . "Beck"^^ . "Susanne Monika Beck"^^ . . . . . . "Molecular pathogenesis and progression of light chain amyloidosis (PDF)"^^ . . . "Beck_Susanne_18_03_1985_Dissertation.pdf"^^ . . . "Molecular pathogenesis and progression of light chain amyloidosis (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Molecular pathogenesis and progression of light chain amyloidosis (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Molecular pathogenesis and progression of light chain amyloidosis (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Molecular pathogenesis and progression of light chain amyloidosis (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Molecular pathogenesis and progression of light chain amyloidosis (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #31632 \n\nMolecular pathogenesis and progression of light chain amyloidosis\n\n" . "text/html" . . . "000 Allgemeines, Wissenschaft, Informatik"@de . "000 Generalities, Science"@en . . . "610 Medizin"@de . "610 Medical sciences Medicine"@en . .