Friday, December 23, 2005


Somebody recently asked on the ACOR List CD38 and VH genes interalate. Let's first think about CD38. It has been mentioned in well over 1000 articles in the past five years, so what is it?

It is a type II transmembrane glycoprotein, the extracellular domain acting as an ectoenzyme, catalyzing the conversion of NAD+ into nicotinamide, ADP-ribose (ADPR) and cyclic ADPR.

That means almost nothing to most people. Let's just say that is a molecule that lives on and in the cell membrane and it is an enzyme; that is, it catalyzes chemical reactions.

It is found on many types of cells, but we are really interested in its role on B-lymphocytes. It is there from time to time as the B cell differentiates (this is a word we introduced yesterday. It means the changes that happen as the cell grows ups from a baby to maturity). It appears on bone marrow precursor cells, but is lost on mature lymphocytes; on germinal center cells it protects against apoptosis, but on leaving the germinal center, memory cells lack the antigen; on terminally differentiated plasma cells it is one of the few surface antigens present. In chronic lymphocytic leukemia (CLL) expression of CD38 signifies a poor prognosis although it does not correlate precisely with the presence of unmutated immunoglobulin variable region (IgV) genes and it may vary during the course of the disease.

Is it more than a prognostic marker? Dr Malavasi and his colleagues in Turin think that CD38 is involved in signaling through the B-cell receptor (BCR).

When we published out first paper on VH genes as prognostic markers, the accompanying paper from Nick Chiorazzi's group in Long Island confirmed our finding and also suggested that CD38 (which is much easier to measure) could act as a surrogate because it gave the same answer.

When we looked at CD38 in our series it gave a very similar answer, but in idividual cases there was a 30% disparity between CD38 levels and VH gene mutations. Those who were discordant for VH genes and CD38, whether it was CD38 positive and VH mutated or CD38 negative and VH unmutated had an average survival midway between the 8 years and 25 years that we had found for mutated versus unmutated. It was 15 years.

The other surprising thing was that of 40 patients in whom we were to follow for a long time we found that the CD38 level changed. Why this was so is complicated. We know that some cytokines like IL-2 and interferon gamma can alter the level of CD38 present, but we also know that after treatment the cells that remain (those resistant to the drugs) often show more CD38 present


johnl said...

Terry: is it known if the 40 patients who's CD38 levels changed were of the IVGH mutated or unmutated subtypes?

Kurt Grayson said...

Sounds like they must have been both mutated and unmutated subtypes because if they followed just one side of the coin, they would always wonder what happened to the other side.


Terry Hamblin said...

There were 10 patients whose levels changed and they were a mixture of mutated and unmutated.

Anonymous said...

I am coming back to this post as people are still not understanding what % of CD38 makes one positive. Some paper's state it is 30%, but should be 20% or even lower. Some say below 20% is a negative result--between 20% and 30% an intermediate result, and above 30% positive. Tom's CD38 at dx was 1%. FCR completed in Dec 2004 and CD38 has been rising. Last flow--6 months ago showed CD38 at 27%. Still negative, correct? Can it go back to 1%?