FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2988312345> ?p ?o ?g. }

• W2988312345 endingPage "1748" @default.
• W2988312345 startingPage "1748" @default.
• W2988312345 abstract "[Introduction] AL amyloidosis is caused by the deposition of abnormally folded clonal immunoglobulin (IG) light chains (LCs, λ:κ = 3:1) made by malignant plasma cells in the bone marrow (BM), which leads to multi-organ dysfunction, often involving the heart, kidney, liver, skin, and nerves. However, little is known about what regulates organ tropism of amyloid deposition in this disease. In addition, no study has analyzed the repertoire of IG germlines of plasma cells in the BM in AL amyloidosis using next generation sequencing (NGS). In this study, we aimed to identify the clonal composition of IG λ light-chain variable region (IGLV) genes in BM cells in patients with AL amyloidosis using NGS. [Material and method] BM cells were obtained at diagnosis from 38 patients with AL amyloidosis and those with other plasma cell disorders: multiple myeloma (MM, n = 7), and monoclonal gammopathy of undetermined significance (MGUS, n = 11) with λ-type monoclonal paraprotein. Seven normal control (NC) patients had either immune thrombocytopenia or malignant lymphoma without BM invasion. Genomic DNA was extracted from the BM mononuclear cells preserved in LABO Banker1 or BM clots in O.C.T compound using QIAamp DNA Blood Mini kit. The IGLV1 and IGLV2 genes were amplified by polymerase chain reaction using a 5′ primer for the IGLV1/2 framework 3 (FR3) region and 3′ consensus primers for the IGLJ1/2/3 joining regions. Multiple samples were pooled, and paired-end 2 × 250 base pair sequencing reactions were performed using an Illumina MiSeq sequencer and then analyzed by an open-source program called Vidjil. All subjects provided written informed consent to participate in the study, in accordance with the Declaration of Helsinki. This study was approved by the ethics committee of the Chiba University Graduate School of Medicine and Japanese Red Cross Medical Center. [Results] Clinical and laboratory features of 38 patients with AL amyloidosis were as follows: primary AL amyloidosis (n = 31); 15 and 20 patients had cardiac and renal dysfunctions, respectively, and secondary AL amyloidosis with MM (n = 7); 4 and 1 patient had cardiac and renal dysfunctions, respectively. In patients with AL amyloidosis, the median plasma cell count in BM aspirate smears was 3.3% (0.1%-50.4%), and the median difference in involved and uninvolved light chains (dFLC) was 104.5 mg/L (28.5mg/L -2673.3mg/L). Representative results of the Vidjil analysis in NC, MGUS, AL amyloidosis, and MM are shown in Figure 1. The most abundant IGLV gene accounted for not >1% of the reads, and there was no dominant germline in NC samples. Therefore, we defined the dominant clone as >1% of IG germlines in plasma cells. According to this definition, clonal IG germlines were found in 27 of 31 patients with primary AL amyloidosis (87%), 5 of 7 with secondary AL amyloidosis (71%), 7 of 7 with MM (100%), and 8 of 11 with MGUS (73%). However, the size of clones in AL amyloidosis (median 3.1%, 0.38%-14.3%) was significantly smaller than that in MM (median 17.8%, 2.2%-17.9%) (P<0.001), and similar to that in MGUS (median 3.8%, 0.4%-32.0%). Importantly, in patients with AL amyloidosis, the dFLC and involved/uninvolved FLC ratio was not correlated with the clonal size of plasma cells in our repertoire analysis using NGS, suggesting that small malignant clones of plasma cells may secret FLC and cause LC depositions in AL amyloidosis. Regarding IGLV germline usage, IGLV1-51 was the most frequent repertoire in AL amyloidosis with heart dysfunction (7 of 16 cases) and renal dysfunction (7 of 21 cases). No relationship between the IGLV germlines and organ tropisms was observed. [Conclusion] We successfully identified the clonal composition of IGLV genes in the BM of most patients with AL amyloidosis using NGS, according to the differences in the V and J region recombination and CDR3 sequences using the Vidjil program. In AL amyloidosis, the clonal size of plasma cells in the BM is small and small malignant clones of plasma cells may secret FLC and cause LC depositions in AL amyloidosis. Figure 1 Disclosures Suzuki: Ono: Research Funding; BMS: Honoraria, Research Funding; Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria." @default.
• W2988312345 created "2019-11-22" @default.
• W2988312345 creator A5000685038 @default.
• W2988312345 creator A5004483807 @default.
• W2988312345 creator A5010181517 @default.
• W2988312345 creator A5014431889 @default.
• W2988312345 creator A5017220667 @default.
• W2988312345 creator A5026218407 @default.
• W2988312345 creator A5027496527 @default.
• W2988312345 creator A5041668258 @default.
• W2988312345 creator A5041674771 @default.
• W2988312345 creator A5047821211 @default.
• W2988312345 creator A5048967405 @default.
• W2988312345 creator A5062040392 @default.
• W2988312345 creator A5068249765 @default.
• W2988312345 creator A5078839273 @default.
• W2988312345 creator A5079640536 @default.
• W2988312345 creator A5081519082 @default.
• W2988312345 creator A5082010384 @default.
• W2988312345 creator A5085289666 @default.
• W2988312345 creator A5089012786 @default.
• W2988312345 creator A5090506661 @default.
• W2988312345 date "2019-11-13" @default.
• W2988312345 modified "2023-09-30" @default.
• W2988312345 title "Identification of Clonal Immunoglobulin λ Light-Chain Gene Rearrangements in AL Amyloidosis Using Next Generation Sequencing" @default.
• W2988312345 doi "https://doi.org/10.1182/blood-2019-125028" @default.
• W2988312345 hasPublicationYear "2019" @default.
• W2988312345 type Work @default.
• W2988312345 sameAs 2988312345 @default.
• W2988312345 citedByCount "0" @default.
• W2988312345 crossrefType "journal-article" @default.
• W2988312345 hasAuthorship W2988312345A5000685038 @default.
• W2988312345 hasAuthorship W2988312345A5004483807 @default.
• W2988312345 hasAuthorship W2988312345A5010181517 @default.
• W2988312345 hasAuthorship W2988312345A5014431889 @default.
• W2988312345 hasAuthorship W2988312345A5017220667 @default.
• W2988312345 hasAuthorship W2988312345A5026218407 @default.
• W2988312345 hasAuthorship W2988312345A5027496527 @default.
• W2988312345 hasAuthorship W2988312345A5041668258 @default.
• W2988312345 hasAuthorship W2988312345A5041674771 @default.
• W2988312345 hasAuthorship W2988312345A5047821211 @default.
• W2988312345 hasAuthorship W2988312345A5048967405 @default.
• W2988312345 hasAuthorship W2988312345A5062040392 @default.
• W2988312345 hasAuthorship W2988312345A5068249765 @default.
• W2988312345 hasAuthorship W2988312345A5078839273 @default.
• W2988312345 hasAuthorship W2988312345A5079640536 @default.
• W2988312345 hasAuthorship W2988312345A5081519082 @default.
• W2988312345 hasAuthorship W2988312345A5082010384 @default.
• W2988312345 hasAuthorship W2988312345A5085289666 @default.
• W2988312345 hasAuthorship W2988312345A5089012786 @default.
• W2988312345 hasAuthorship W2988312345A5090506661 @default.
• W2988312345 hasConcept C142724271 @default.
• W2988312345 hasConcept C153911025 @default.
• W2988312345 hasConcept C159654299 @default.
• W2988312345 hasConcept C163864487 @default.
• W2988312345 hasConcept C203014093 @default.
• W2988312345 hasConcept C2776364478 @default.
• W2988312345 hasConcept C2776396001 @default.
• W2988312345 hasConcept C2777250017 @default.
• W2988312345 hasConcept C2779551797 @default.
• W2988312345 hasConcept C2779951007 @default.
• W2988312345 hasConcept C2780007613 @default.
• W2988312345 hasConcept C2780411336 @default.
• W2988312345 hasConcept C3020196193 @default.
• W2988312345 hasConcept C36394416 @default.
• W2988312345 hasConcept C542903549 @default.
• W2988312345 hasConcept C71924100 @default.
• W2988312345 hasConcept C86803240 @default.
• W2988312345 hasConceptScore W2988312345C142724271 @default.
• W2988312345 hasConceptScore W2988312345C153911025 @default.
• W2988312345 hasConceptScore W2988312345C159654299 @default.
• W2988312345 hasConceptScore W2988312345C163864487 @default.
• W2988312345 hasConceptScore W2988312345C203014093 @default.
• W2988312345 hasConceptScore W2988312345C2776364478 @default.
• W2988312345 hasConceptScore W2988312345C2776396001 @default.
• W2988312345 hasConceptScore W2988312345C2777250017 @default.
• W2988312345 hasConceptScore W2988312345C2779551797 @default.
• W2988312345 hasConceptScore W2988312345C2779951007 @default.
• W2988312345 hasConceptScore W2988312345C2780007613 @default.
• W2988312345 hasConceptScore W2988312345C2780411336 @default.
• W2988312345 hasConceptScore W2988312345C3020196193 @default.
• W2988312345 hasConceptScore W2988312345C36394416 @default.
• W2988312345 hasConceptScore W2988312345C542903549 @default.
• W2988312345 hasConceptScore W2988312345C71924100 @default.
• W2988312345 hasConceptScore W2988312345C86803240 @default.
• W2988312345 hasIssue "Supplement_1" @default.
• W2988312345 hasLocation W29883123451 @default.
• W2988312345 hasOpenAccess W2988312345 @default.
• W2988312345 hasPrimaryLocation W29883123451 @default.
• W2988312345 hasRelatedWork W1252457205 @default.
• W2988312345 hasRelatedWork W1608930163 @default.
• W2988312345 hasRelatedWork W2091228530 @default.
• W2988312345 hasRelatedWork W2106258434 @default.
• W2988312345 hasRelatedWork W2120884623 @default.
• W2988312345 hasRelatedWork W2151112811 @default.
• W2988312345 hasRelatedWork W3118048457 @default.
• W2988312345 hasRelatedWork W3208416834 @default.
• W2988312345 hasRelatedWork W4290698720 @default.

• next