Hepatocyte growth factor is essential to keep CLL cells alive

It is well known that CLL cells survive better in the body than outside it. This is thought to be caused by cell contact with stromal cells of some sort, but the exact mechanism is unclear. Now an interesting paper from Italy sheds some light on it. (incidentally I have identified Italy where they have spent a lot of public money on CLL research as a place where good papers seem to be coming from, but perhaps signor Berlesconi has been a bit rash?)

They have used various types of tissues to stabilize CLL cells in cell culture. Human bone marrow stromal cells, fibroblasts, trabecular bone derived cells and an osteoblast like cell line enhanced the survival of leukemic cells but endothelial cells and chondrocytes did not. Gene expression profile analysis identified two soluble factors, hepatocyte growth factor and CXCL12, that were produced only by the mesenchymal lineages that sustain CLL cells. Indeed CLL cells express a functional receptor gor hepatocyte growth factor (c-MET). They demonstrated that hepatocyte growth factor enhanced the viability of CLL cells through STAT3 phosphorylation which can be blocked by a c-MET TKI. The use of si-RNA knockdown of Hepatocyte growth factor in mesenchymal cells confirmed the interaction.

Whether this might of might not be a safe target for therapy is an open question. What would it do to the liver? And would CXCL12 also have to be targeted.