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000274226 1001_ $$00000-0002-6910-7792$$aVom Stein, Alexander F$$b0
000274226 245__ $$aLYN kinase programs stromal fibroblasts to facilitate leukemic survival via regulation of c-JUN and THBS1.
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000274226 520__ $$aMicroenvironmental bystander cells are essential for the progression of chronic lymphocytic leukemia (CLL). We have discovered previously that LYN kinase promotes the formation of a microenvironmental niche for CLL. Here we provide mechanistic evidence that LYN regulates the polarization of stromal fibroblasts to support leukemic progression. LYN is overexpressed in fibroblasts of lymph nodes of CLL patients. LYN-deficient stromal cells reduce CLL growth in vivo. LYN-deficient fibroblasts show markedly reduced leukemia feeding capacity in vitro. Multi-omics profiling reveals that LYN regulates the polarization of fibroblasts towards an inflammatory cancer-associated phenotype through modulation of cytokine secretion and extracellular matrix composition. Mechanistically, LYN deletion reduces inflammatory signaling including reduction of c-JUN expression, which in turn augments the expression of Thrombospondin-1, which binds to CD47 thereby impairing CLL viability. Together, our findings suggest that LYN is essential for rewiring fibroblasts towards a leukemia-supportive phenotype.
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000274226 7001_ $$00000-0002-8910-867X$$aRebollido-Rios, Rocio$$b1
000274226 7001_ $$aLukas, Anna$$b2
000274226 7001_ $$aKoch, Maximilian$$b3
000274226 7001_ $$avon Lom, Anton$$b4
000274226 7001_ $$aReinartz, Sebastian$$b5
000274226 7001_ $$aBachurski, Daniel$$b6
000274226 7001_ $$aRose, France$$b7
000274226 7001_ $$00000-0002-0917-6876$$aBozek, Katarzyna$$b8
000274226 7001_ $$aAbdallah, Ali T$$b9
000274226 7001_ $$aKohlhas, Viktoria$$b10
000274226 7001_ $$aSaggau, Julia$$b11
000274226 7001_ $$aZölzer, Rebekka$$b12
000274226 7001_ $$aZhao, Yue$$b13
000274226 7001_ $$aBruns, Christiane$$b14
000274226 7001_ $$00000-0001-9662-9900$$aBröckelmann, Paul J$$b15
000274226 7001_ $$aLohneis, Philipp$$b16
000274226 7001_ $$00000-0001-8806-4786$$aBüttner, Reinhard$$b17
000274226 7001_ $$0P:(DE-He78)2d1f34b41ac62ef6f3c9f5b3ad4c4ed8$$aHäupl, Björn$$b18$$udkfz
000274226 7001_ $$0P:(DE-He78)6fe098b268bbad1a939e14ed018b295f$$aOellerich, Thomas$$b19$$udkfz
000274226 7001_ $$00000-0002-3249-7264$$aNguyen, Phuong-Hien$$b20
000274226 7001_ $$00000-0002-7425-4455$$aHallek, Michael$$b21
000274226 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-023-36824-2$$gVol. 14, no. 1, p. 1330$$n1$$p1330$$tNature Communications$$v14$$x2041-1723$$y2023
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