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@ARTICLE{VomStein:274226,
author = {A. F. Vom Stein and R. Rebollido-Rios and A. Lukas and M.
Koch and A. von Lom and S. Reinartz and D. Bachurski and F.
Rose and K. Bozek and A. T. Abdallah and V. Kohlhas and J.
Saggau and R. Zölzer and Y. Zhao and C. Bruns and P. J.
Bröckelmann and P. Lohneis and R. Büttner and B.
Häupl$^*$ and T. Oellerich$^*$ and P.-H. Nguyen and M.
Hallek},
title = {{LYN} kinase programs stromal fibroblasts to facilitate
leukemic survival via regulation of c-{JUN} and {THBS}1.},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2023-00512},
pages = {1330},
year = {2023},
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.},
cin = {FM01},
ddc = {500},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36899005},
pmc = {pmc:PMC10006233},
doi = {10.1038/s41467-023-36824-2},
url = {https://inrepo02.dkfz.de/record/274226},
}