TY  - JOUR
AU  - Vom Stein, Alexander F
AU  - Rebollido-Rios, Rocio
AU  - Lukas, Anna
AU  - Koch, Maximilian
AU  - von Lom, Anton
AU  - Reinartz, Sebastian
AU  - Bachurski, Daniel
AU  - Rose, France
AU  - Bozek, Katarzyna
AU  - Abdallah, Ali T
AU  - Kohlhas, Viktoria
AU  - Saggau, Julia
AU  - Zölzer, Rebekka
AU  - Zhao, Yue
AU  - Bruns, Christiane
AU  - Bröckelmann, Paul J
AU  - Lohneis, Philipp
AU  - Büttner, Reinhard
AU  - Häupl, Björn
AU  - Oellerich, Thomas
AU  - Nguyen, Phuong-Hien
AU  - Hallek, Michael
TI  - LYN kinase programs stromal fibroblasts to facilitate leukemic survival via regulation of c-JUN and THBS1.
JO  - Nature Communications
VL  - 14
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2023-00512
SP  - 1330
PY  - 2023
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:36899005
C2  - pmc:PMC10006233
DO  - DOI:10.1038/s41467-023-36824-2
UR  - https://inrepo02.dkfz.de/record/274226
ER  -