The latest video From Andrew Schorr and Patient Power
Dr. William Wierda of MD Anderson discusses the recent data releases at ASH this year Offering some interesting thoughts about some of those still in remission after 9 years post FCR.
"MD Anderson Cancer Center in Houston pioneered the use of fludarabine + cyclophosphamide + rituximab (FCR) for the treatment of chronic lymphocytic leukemia (CLL). Now researchers have been analyzing the data of patients treated as far back as 1999, and the news--for many--is good. For patients who remain in remission over nine years, there is now discussion about whether they may, in fact, be cured. This is the first time the word "cure" has been discussed related to a chemo-based regimen. Dr. William Wierda, a leading CLL researcher, explains the latest study results". - See more at: patientpower.info/video/is-...
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Note ...up until recently the gene was call IgVH. Then the name was changed to IGHV.
There are a number of genes in a cluster, so the family of genes is written as IGHV@.
If you are searching on Google, older articles will be found using igvh, new articles ighv.
...
IGHV... Immunoglobulin g heavy chain V-III region VH26 is a protein that in humans is encoded by the IGHV@ family of gene.
....
'The mutation status of the IgVH gene is also an important prognostic factor tested in the blood. IgVH genes, found in the DNA of lymphocytes, are responsible for producing antibodies. A mutated IgVH gene is a good prognostic factor.
The more mutated IgVH genes are, the more mature the genes are, making them more capable of protecting the body. CLL patients with mutated genes typically have a less aggressive course of disease and require treatment later than CLL patients whose lymphocytes contain unmutated genes.
An unmutated IgVH gene is related to earlier disease progression and a shorter remission.'
About 70% of CLL falls into one of two groups...mutated, have slower disease and longer survival, unmutated, have shorter time to treatment, more aggressive disease and shorter survival.
But there are other factors... it is a family of genes, so WHICH gene is used to drive CLL, is as or more important than the mutation factor...
There is a direct test for IGHV mutation status and gene driver number, but it is extremely expensive and is rarely done outside major CLL research centers...
However, we have a cheap test, called Flow Cytometry, that every CLL patient has had done at diagnosis. A cell surface protein, called CD38, is a good indicator of IGHV mutation status... so clinically CD38 is used... as a prognostic marker.
If your CD38 is under 30% your IGHV gene is likely mutated. If the percent is over 30% the gene is likely unmutated. This CD38 is called a marker and is about 70% correct. Further, the percent changes over time, but rarely goes over or under the 30% mark.
There is another marker called Zap70 but it is problematic, unless done in a CLL research lab, so it may or may not agree with CD38, which adds more confusion.
In the clinic, Zap70 is falling out of favour as a test.
There is lots about this gene on the internet, but it is a highly complex topic...
Chris thanks for a great overview and explaination..
Below are a few links that may help but as Chris says it is hard to get your head around, it takes a bit of time.
Early research was able to show that the amount of IGHV mutation present in CLL clones varies between different patients it was discovered patients with unmutated IGHV genes may have more chance of a worse prognosis than those with mutated IGHV genes.
As more of the picture has unfolded more is now understood about the influence of other mutations too, there is discordance allowing the reverse to be true too. As Chris says other markers are also used as surrogates that may correlate with IGHV mutational status..
These are good articles written by Chaya Venkat at CLL topics that explain this marker and its significance. It is quite a hard topic to get your head around, Chris's summary above is one of the best I've read. updates.clltopics.org/3695-... and clltopics.org/PI/Type.htm
Here is another of Chaya’s articles from last year that explains prognostic markers and the definitive recent paper by UK clinical researchers explaining which markers are useful in early CLL prognostics. IGHV mutational status may also be useful with others as a prognostic marker in predicting time to first treatment. However in the UK testing may not be available to patients in some NHS trusts ahead of treatment. updates.clltopics.org/4336-...
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