Other Distinctive Phenotypic Features

In addition to the HC-"restricted" activation antigens alluded to above, global gene-expression analysis has identified a large number of new genes differentially expressed by HCs as compared to normal memory B cells and a range of normal and malignant B-cell-types.4 Genes of particular potential importance identified by this technology include those related to HC morphology, to the long-known "monocytic" features of HCs, to the adhesion and homing of the malignant cells, and to their propensity to alter the extracellular matrix of bone marrow and hepatic portal tracts. These phenotypic features are listed in Table 29.3 and will be

Table 29.3 Newly identified differentially expressed genes of potential pathogenetic importance

Morphology related pp52 (LSP-1), p-actin, Gas 7 and EPB4.IL-2

'"Monocytic" features annexin 1, CD63, CPVL, CD68, c-Maf

Unusual tissue distribution CCR7 and CXCR5 chemokine receptors downregulated TIMP-1, TIMP-4 and RECK matrix metalloproteinase inhibitors upregulated

Matrix remodeling Overexpression of FGF-2 and FGFR1 confirm previous evidence for involvement of this autocrine loop in the stimulation of the production of HC-derived fibronectin responsible for the bone marrow fibrosis of HCL

considered further in the section dealing with the pathology of the disease.

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