It has long been known that CLL cells need help to be able to survive. Several studies have shown that it is what goes on in the tissues rather than the blood that provides the drive for CLL cells to multiply and resist apoptosis. A number of different cells have been implicated including 'nurse' cells described by Tom Kipps group and T cells according to Sylbia Deaglio's group in Italy.
I have been going back through old copies of Blood before disposing of them and I came across this article in the issue from November 18th last year. Soluble CD14 is a novel monocyte-derived survival factor for chronic lymphocytic leukemia cells, which is induced by CLL cells in vitro and present at abnormally high levels in vivo by Martina Seiffert, Angela Schulz, Sibylle Ohl, Hartmut Dohner, Stephan Stilgenbauer, and Peter Lichter. Ulm, Germany
The bottom line is that monocytes help in the survival of CLL cells by secreting soluble CD14, which induces nuclear factor kappa B activation in these cells, and that CLL cells actively shape their microenvironment by inducing CD14 secretion in accessory monocytes.
CD14 is a cell-surface receptor present on monocytes and macrophages, and to a lesser extent on neutrophils and dendritic cells. By binding bacterial Lipopolysaccharide (LPS), CD14 helps in the activation of Toll-like receptor (TLR)-4 signaling, which subsequently results in the activity of NF kappa B, AP1, and IRF3 transcription factors. Although LPS is considered its main ligand, CD14 also recognizes other pathogen associated molecules. A soluble form of CD14 is present in body fluids, like blood, saliva or breast milk, where it is involved in innate immunity by conferring its signaling activity to cells that do not express CD14. By adding recombinant soluble CD14 to CLL cells in culture, they observed increased CLL cell viability. Consistent with this they found that stimulation of CLL cells with soluble CD14 resulted in an augmented activity of the NF Kappa B components, p50 and p65, which are known to be constitutively active in primary CLL cells and are associated with their survival.
It is known that soluble CD14 is raised in patients with CLL and that it parallels the B-cell count.
Another possible target for treatment?
I know a lot of natural products can supposedly curb NFkB activity, curcumin among them.
ReplyDeleteAre there any such agents that are readily obtained that might help CLLers?
(A friend who has multiple myeloma swears by curcumin; she's been on it for several years. She has a blog.)