Bone Marrow

The bone marrow (BM) is variably infiltrated by widely spaced HCs surrounded by clear areas, which impart a halo appearance. This loose packing probably reflects cell spreading on the altered ECM and has been likened to a fried-egg appearance.42 This appearance is also seen when HCs adhere to FN-coated surfaces in vitro.43

In the BM microenvironment, the FN component of the distinctive reticulin fibrosis is largely, if not exclusively, synthesized by HCs themselves.22 30 As mentioned above, adhesion receptors, together with autocrine bFGF, play a key role in this matrix remodeling. It has been demonstrated that in BM and hepatic portal tracts adhesion to hyaluronan via the standard hematopoietic form of CD44 stimulates HCs to secrete bFGF.30 This bFGF binds to both FGFR1 and CD44v3 on HCs and stimulates them to produce FN.30 Secreted FN is then assembled into a matrix by a process involving a5pi FN receptors on the malignant cells.22 The importance of HA for the initiation of this process is indicated by the absence of fibrosis in the infiltrated red pulp of the spleen, which does not contain HA.

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