Journal Article

DKFZ-2023-00512

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png LYN kinase programs stromal fibroblasts to facilitate leukemic survival via regulation of c-JUN and THBS1.

Vom Stein, A. F. ; Rebollido-Rios, R. ; Lukas, A. ; Koch, M. ; von Lom, A. ; Reinartz, S. ; Bachurski, D. ; Rose, F. ; Bozek, K. ; Abdallah, A. T. ; Kohlhas, V. ; Saggau, J. ; Zölzer, R. ; Zhao, Y. ; Bruns, C. ; Bröckelmann, P. J. ; Lohneis, P. ; Büttner, R. ; Häupl, B.DKFZ* ; Oellerich, T.DKFZ* ; Nguyen, P.-H. ; Hallek, M.

2023
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-023-36824-2

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.

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Contributing Institute(s):

1. DKTK FM zentral (FM01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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