LYN kinase programs stromal fibroblasts to facilitate leukemic survival via regulation of c-JUN and THBS1

Alexander F. vom Stein, Rocio Rebollido-Rios, Anna Lukas, Maximilian Koch, Anton Lom, Sebastian Reinartz, Daniel Bachurski, France Rose, Katarzyna Bozek, Ali T. Abdallah, Viktoria Kohlhas, Julia Saggau, Rebekka Zölzer, Yue Zhao, Christiane Bruns, Paul J. Bröckelmann, Philipp Lohneis, Reinhard Büttner, Björn Häupl, Thomas Oellerich, Phuong-Hien Nguyen () and Michael Hallek ()
Additional contact information
Alexander F. vom Stein: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf
Rocio Rebollido-Rios: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf
Anna Lukas: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf
Maximilian Koch: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf
Anton Lom: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf
Sebastian Reinartz: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf
Daniel Bachurski: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf
France Rose: University of Cologne
Katarzyna Bozek: University of Cologne
Ali T. Abdallah: University of Cologne
Viktoria Kohlhas: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf
Julia Saggau: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf
Rebekka Zölzer: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf
Yue Zhao: University of Cologne
Christiane Bruns: University of Cologne
Paul J. Bröckelmann: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf
Philipp Lohneis: Hämatopathologie Lübeck
Reinhard Büttner: University of Cologne
Björn Häupl: Johann Wolfgang Goethe University
Thomas Oellerich: Johann Wolfgang Goethe University
Phuong-Hien Nguyen: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf
Michael Hallek: Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf

Nature Communications, 2023, vol. 14, issue 1, 1-22

Abstract: Abstract Microenvironmental bystander cells are essential for the progression of chronic lymphocytic leukemia (CLL). We have discovered previously that LYN kinase promotes the formation of a microenvironmental niche for CLL. Here we provide mechanistic evidence that LYN regulates the polarization of stromal fibroblasts to support leukemic progression. LYN is overexpressed in fibroblasts of lymph nodes of CLL patients. LYN-deficient stromal cells reduce CLL growth in vivo. LYN-deficient fibroblasts show markedly reduced leukemia feeding capacity in vitro. Multi-omics profiling reveals that LYN regulates the polarization of fibroblasts towards an inflammatory cancer-associated phenotype through modulation of cytokine secretion and extracellular matrix composition. Mechanistically, LYN deletion reduces inflammatory signaling including reduction of c-JUN expression, which in turn augments the expression of Thrombospondin-1, which binds to CD47 thereby impairing CLL viability. Together, our findings suggest that LYN is essential for rewiring fibroblasts towards a leukemia-supportive phenotype.

Date: 2023
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36824-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36824-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36824-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().