Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
138
result(s) for
"Lutz, Raphael"
Sort by:
Resolving the spatial architecture of myeloma and its microenvironment at the single-cell level
In multiple myeloma spatial differences in the subclonal architecture, molecular signatures and composition of the microenvironment remain poorly characterized. To address this shortcoming, we perform multi-region sequencing on paired random bone marrow and focal lesion samples from 17 newly diagnosed patients. Using single-cell RNA- and ATAC-seq we find a median of 6 tumor subclones per patient and unique subclones in focal lesions. Genetically identical subclones display different levels of spatial transcriptional plasticity, including nearly identical profiles and pronounced heterogeneity at different sites, which can include differential expression of immunotherapy targets, such as CD20 and CD38. Macrophages are significantly depleted in the microenvironment of focal lesions. We observe proportional changes in the T-cell repertoire but no site-specific expansion of T-cell clones in intramedullary lesions. In conclusion, our results demonstrate the relevance of considering spatial heterogeneity in multiple myeloma with potential implications for models of cell-cell interactions and disease progression.
The spatial architecture of multiple myeloma remains to be explored. Here, the authors perform bulk and single cell sequencing for samples from newly diagnosed patients and reveal gene signatures associated with focal lesions and spatial heterogeneity in the tumour microenvironment.
Journal Article
Rescuing the vulnerable
In many ways, the European welfare state constituted a response to the new forms of social fracture and economic turbulence that were born out of industrialization—challenges that were particularly acute for groups whose integration into society seemed the most tenuous. Covering a range of national cases, this volume explores the relationship of weak social ties to poverty and how ideas about this relationship informed welfare policies in the nineteenth and twentieth centuries. By focusing on three representative populations—neglected children, the homeless, and the unemployed—it provides a rich, comparative consideration of the shifting perceptions, representations, and lived experiences of social vulnerability in modern Europe.
eBook
Multiple myeloma long-term survivors exhibit sustained immune alterations decades after first-line therapy
The long-term consequences of cancer and its therapy on the patients’ immune system years after cancer-free survival remain poorly understood. Here, we present an in-depth characterization of the bone marrow immune ecosystem of multiple myeloma long-term survivors, from initial diagnosis up to 17 years following a single therapy line and cancer-free survival. Using comparative single-cell analyses combined with molecular, genomic, and functional approaches, we demonstrate that multiple myeloma long-term survivors exhibit pronounced alterations in their bone marrow microenvironment associated with impaired immunity. These immunological alterations were frequently linked to an inflammatory immune circuit fueled by the long-term persistence or resurgence of residual myeloma cells. Notably, even in the complete absence of any detectable residual disease for decades, sustained changes in the immune system were observed, suggesting an irreversible ‘immunological scarring’ caused by the initial exposure to the cancer and therapy. Collectively, our study provides key insights into the molecular and cellular bone marrow ecosystem of long-term survivors of multiple myeloma, revealing both reversible and irreversible alterations in the immune compartment.
Understanding the immunological underpinnings of long-term survival in cancer is of high interest. Here, authors dissect the immune parameters of multiple myeloma long-term survivors following a single line of therapy longitudinally, and find sustained changes, including inflammation and impaired immune function.
Journal Article
Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states
Single-cell genomics technology has transformed our understanding of complex cellular systems. However, excessive cost and a lack of strategies for the purification of newly identified cell types impede their functional characterization and large-scale profiling. Here, we have generated high-content single-cell proteo-genomic reference maps of human blood and bone marrow that quantitatively link the expression of up to 197 surface markers to cellular identities and biological processes across all main hematopoietic cell types in healthy aging and leukemia. These reference maps enable the automatic design of cost-effective high-throughput cytometry schemes that outperform state-of-the-art approaches, accurately reflect complex topologies of cellular systems and permit the purification of precisely defined cell states. The systematic integration of cytometry and proteo-genomic data enables the functional capacities of precisely mapped cell states to be measured at the single-cell level. Our study serves as an accessible resource and paves the way for a data-driven era in cytometry.
Haas, Velten and colleagues use single-cell multiomics of human blood and bone marrow to generate a reference map allowing the quantitative linking of cytometry and proteo-genomic information.
Journal Article
Arbeitsbiografien und Strukturwandel „nach dem Boom”: Lebensläufe und Berufserfahrungen britischer, französischer und westdeutscher Industriearbeiter und -arbeiterinnen von 1970 bis 2000
The article compares life courses and work biographies of industrial workers in West Germany, France and Britain during the period of de-industrialization between the mid-1970s and the year 2000. It discusses continuities and changes of specific patterns in the work biographies of male skilled and unskilled workers, of young people entering the shrinking job market, of migrant workers, and of women. It also analyzes the effects of mass unemployment, of early retirement schemes and of different systems of general and professional education in the three Western European countries.
Journal Article
