The EHA meeting is on just now in Copenhagen. I went to Copenhagen on Thursday but only to attend the European Research Initiative on CLL (ERIC) meeting that was held at the same time and to co-host the Leukemia Research dinner in the evening.
Copenhagen is the largest Scandinavian city and as one would expect, clean, very white, and traffic-free. The public transport system is outstanding and fun to negotiate. The language is unintelligible but virtually everybody speaks English very well. Because I booked late, I had to stay in a remote Zleep hotel, but it was cheap, clean and functional. The only drawback was its distance from the center, but the trip by train, metro and bus was easy to work out and remarkably quick.
At the ERIC meeting Piers Patten presented his confocal microscopy work on CD38 in proliferation centers. As I played some small part in this I was glad to see it presented and I think I have already blogged about it, as I have about Christian Plass and John Byrd's work on DAPK in familial CLL.
There was a good presentation by John Gribben on The impact of microenvironment crosstalk for cell survival in CLL. This has also been recently published on-line at J Clin Invest .
Life in the proliferation center is fine for the CLL cell. The crosstalk between the CLL cell and the normal cells ensures that the CLL cells stays alive and proliferates while the normal cells functions poorly. The immune system is switched off. One of the effects is that the CLL cell is not rejected, but also immunity to pathogens is suppressed. John's paper begins to dissect the mechanisms involved. Engagement of the T-cell receptor should lead to major morphological changes in the T cell, characterized by changes to the actin cytoskeleton and the accumulation of F-actin at the site of contact with the antigen presenting cell (APC). This is termed the immunological synapse. B cells as well as dendritic cells act as APCs and in CLL, the CLL B cell is known to be defective in this respect. Experiments performed by the Gribben group demonstrated that autologous CD4+ and CD8+ cells from CLL patients have impaired actin polymerization at the immunological synapse; that defects in both B and T cells contribute to this; that CLL cells induce defective immunological synapse formation in healthy allogeneic T cells, that CLL cells induce defective recruitment of immunological synapse signaling molecules such as the integrin LFA-1, the tyrosine kinase Lck, and the actin regulatory proteins Cdc42, WASp, filamin-A and dynamin-2; that CLL T cells have reduced activation and effector function; and that the drug lenalidomide enhances autologous immune synapse formation in CLL.
Understanding what is going on in the proliferation center is integral to understanding CLL, and it is clear that this understanding has been enhanced by John Gribben's excellent work. American readers might be pleased to hear that John has just been elected to the Academy of Medical Sciences, the premier body in medical science in the UK. He becomes the fifth CLL specialist to be elected (after Freda Stevenson, John Cawley, Daniel Catovsky and myself). The Academy has about 800 members from across medical science.