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BM fibroblast

sCD23. TGF-ß. SDF-1. BM fibroblast. Long survival of B-CLL cells in vivo. Exogenous survival signal Cytokines, Growth factors Adhesion molecules. Endogenous defect : bcl-2, TGF-ß CD23, Notch,. B-CLL. CD44. Hyaluronan. VLA-4. Fibronectin. VLA-5. VCAM-1.

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BM fibroblast

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  1. sCD23 TGF-ß SDF-1 BM fibroblast Long survival of B-CLL cells in vivo Exogenous survival signal Cytokines, Growth factors Adhesion molecules Endogenous defect: bcl-2, TGF-ß CD23, Notch, B-CLL CD44 Hyaluronan VLA-4 Fibronectin VLA-5 VCAM-1 A model for B-CLL cell interaction with bone marrow fibroblasts

  2. B-CLL Receptors Cytokines & Growth factors ECM/Adhesion HA IFN-a FN TGF-ß BCR IL-3 IL-4 IL-6 CD19 RTK CD23 CD5 Integrins CD44 Lck Syk,Btk fyn FAK, ILK PI3-K Rho,Rock Ly294002 Wortmannin PIP3 PIP2 PKB/Akt Bcl-2/ Bcl-xl/ Bad Caspase-9 inactive FKHR Fas L IkBK NF-kB (c-IAP1,2) eNOS NO PTEN Tumour supp BRCA1 Tumour supp mTOR/ GSK3 Growth, CC Inhibition of apoptosis

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