Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA352724 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cyclin D1 in AL Amyloidosis Baseline Plasma Cells
| PRJNA130121 | ENA
Project description:Immunoglobulin light chain (AL) amyloidosis is characterized by deposition of abnormal amyloid fibrils in multiple organs impairing their function. CD138-purified plasma cells producing these fibrils are investigated regarding chromosomal alterations by interphase fluorescence in situ hybridization (iFISH) using a multiple myeloma specific probe set for the IgH translocations as well as recurrent numerical aberrations. Aberrations genuine to AL amyloidosis cannot be detected due to the inherent limitation of this probe panel to known loci. We analyzed 118 AL amyloidosis patients by high-density copy number array to quantitatively detect genome-wide chromosomal imbalances. Most prevalent gains affected chromosomes 1q (37%), 9 (24%), 11q (24%), and 19 (16%). The most frequent deletion was monosomy 13 (28%) followed by partial deletions on 14q (21%), 16q (14%), and 13q (12%). The results were analyzed with respect to cytogenetic subgroups. In 88% of patients with translocation t(11;14) and concomitant gain of 11q22.3/11q23 detected by iFISH, the latter aberration was not due to trisomy of chromosome 11 but part of the unbalanced translocation der(14)t(11;14)(q13;q32) with breakpoint in the CCND1/MYEOV gene region. Partial loss of chromosomes 14q and 16q were significantly associated to patients with gain 1q. Our iFISH probe set is highly concordant with copy number results as it detects the most common cytogenetic aberrations present in AL amyloidosis. Beyond that, the probe panel is also the method of choice to detect translocations involving the IgH locus. In contrast to the results of our iFISH panel the frequency of hyperdiploidy detected by copy number array analysis is higher.
2017-03-29 | GSE89616 | GEO
Project description:Phenotypic, transcriptomic and genomic characterization of clonal plasma cells in light chain amyloidosis [Copy number analysis]
| PRJNA296101 | ENA
Project description:AL amyloidosis is a disorder characterized by expansion of clonal plasma cells in the bone marrow and distant end organ damage mediated by misfolded immunoglobulin free light chains. There are currently limited data regarding the functional characteristics of AL amyloidosis plasma cells and their surrounding bone marrow microenvironment. We performed 5’ single cell RNA sequencing on 9 newly diagnosed, treatment naive AL amyloidosis patients and 8 healthy subjects. We identified generalized suppression of normal bone marrow hematopoiesis with distinct expansion of CD16 monocytes and subsets of CD4+ T cells in AL amyloidosis patients. We detected significant transcriptional changes broadly occurring among immune cells with increased interferon α and γ response and decreased TNF-α signaling. T and B cell receptor profiling revealed no overt clonal expansion of B or T cells in AL amyloidosis patients. However, we noted a disproportionate expansion of a distinct population of non-malignant plasma cells in AL amyloidosis patients. Finally, clonal AL amyloidosis plasma cells were identified based on their unique VDJ rearrangement and they showed increased expression of genes involved in proteostasis and antigen processing when compared to autologous, polyclonal plasma cells. Inter-patient transcriptional heterogeneity was evident, with transcriptional states reflective of common genomic translocations easily identifiable. Overall, this study defines the transcriptional characteristics of AL amyloidosis plasma cells and their surrounding bone marrow microenvironment, identifying transcriptional signatures that serve as candidates in early diagnosis in larger studies, and potential molecular targets for therapy.
2025-03-18 | GSE292189 | GEO
Project description:Light chain amyloidosis (AL) is a life-threatening plasma cell dyscrasia manifested by irreversible damage of multiple organs caused by monoclonal immunoglobulin light chain, production of pathogenic bone marrow plasma cells (BMPCs). Although AL is featured by both misfolding of monoclonal protein and plasma cell proliferation, the functional subclones and molecular mechanism of BMPCs in AL remain elusive. Also, inter-individual heterogeneities of AL determine the chemotherapy response and organ tropism of light chains, which require well-defined molecular subtypes. To address these, we conducted single-cell RNA sequencing (scRNA-seq) of BMPCs donated by patients with AL, patients with monoclonal gammopathy of undetermined significance (MGUS), and healthy controls. Single-cell transcriptome revealed a continuity of bone marrow plasma cell (BMPC) functional subclones, delineating DNA repair, cell proliferation, immunoglobulin production, etc., with the gradient of signaling entropy and immunoglobulin production. The amyloidosis-associated genes, such as the amyloid-beta binding Apolipoprotein E (APOE), Cystatin 3 (CST3), and Complement C1q A Chain (C1QA), were up-regulated in a subclone enriched in AL. The speculated light chain-producing subclones in AL up-regulated neutrophil degranulation pathways, transport to and modifications in Golgi apparatus, and asparagine N-linked protein glycosylation. Cyclin D1 (CCND1)hi AL, consisted of larger main subclones which highly expressed Bcl-2 complex and B-cell differentiation genes, was sensitive to venetoclax that targets Bcl-2. A major subset of CCND1low AL harbored larger carbohydrate-synthesizing subclone and up-regulated CCND2 and the amyloidosis-associated genes. Collectively, our results provided frontier insights into the functional subclones and molecular mechanism of BMPCs in AL, associated with amyloidosis, light chain production and venetoclax sensitivity, as knowledge for the future research on AL pathogenesis, AL subtypes and AL-specific therapies.
2022-06-01 | GSE188222 | GEO
Project description:Immunoglobulin light-chain amyloidosis (AL) is a rare clonal plasma cell (PC) disorder that remains largely incurable. AL and multiple myeloma (MM) share the same cellular origin, but while knowledge about MM PC biology has improved significantly, the same does not apply for AL. Here, we undertook an integrative phenotypic, molecular, and genomic approach to study clonal PCs from 22 newly-diagnosed AL patients. Through principal-component-analysis, we demonstrated highly overlapping phenotypic profiles between AL and MGUS or MM patients. However, in contrast to MM, highly-purified FACSs-sorted clonal PCs in AL (n=9/22) show virtually normal transcriptomes with only 68 deregulated genes as compared to normal PCs, including a few tumor suppressor (CDH1, RCAN) and pro-apoptotic (GLIPR1, FAS) genes. Notwithstanding, clonal PCs in AL (n=11/22) were genomically unstable with a median of 9 copy-number-abnormities (CNAs) per case; many of which similar to those found in MM. Whole-exome sequencing (WES) was performed in three AL patients and revealed a median of 10 non-recurrent mutations per case. Altogether, we showed that although clonal PCs in AL display phenotypic and CNA profiles similar to MM, their transcriptome is remarkably similar to that of normal PCs. First-ever WES revealed the lack of a unifying mutation in AL
2016-07-22 | GSE73041 | GEO
Project description:Immunoglobulin light-chain amyloidosis (AL) is a rare clonal plasma cell (PC) disorder that remains largely incurable. AL and multiple myeloma (MM) share the same cellular origin, but while knowledge about MM PC biology has improved significantly, the same does not apply for AL. Here, we undertook an integrative phenotypic, molecular, and genomic approach to study clonal PCs from 22 newly-diagnosed AL patients. Through principal-component-analysis, we demonstrated highly overlapping phenotypic profiles between AL and MGUS or MM patients. However, in contrast to MM, highly-purified FACSs-sorted clonal PCs in AL (n=9/22) show virtually normal transcriptomes with only 68 deregulated genes as compared to normal PCs, including a few tumor suppressor (CDH1, RCAN) and pro-apoptotic (GLIPR1, FAS) genes. Notwithstanding, clonal PCs in AL (n=11/22) were genomically unstable with a median of 9 copy-number-abnormities (CNAs) per case; many of which similar to those found in MM. Whole-exome sequencing (WES) was performed in three AL patients and revealed a median of 10 non-recurrent mutations per case. Altogether, we showed that although clonal PCs in AL display phenotypic and CNA profiles similar to MM, their transcriptome is remarkably similar to that of normal PCs. First-ever WES revealed the lack of a unifying mutation in AL
2016-07-22 | GSE73040 | GEO