CLL Support Association

IGVH Unmutated and Stereotypes

I have a question that I am going to ask my CLL doctor when I see him, but I am wondering if anyone can answer. I am IGVH unmutated, which I understand is correlated with an aggressive disease. Is that true for everyone who unmutated? Or are there some sub-set of unmutated who belong to selected VH families who have an indolent disease? I understand that the mutuational status does not change. I unfortunately have a 0% mutation rate. A “family” was expressed on my IGVH test results, but I cannot recall which it is. Finally, I am wondering when CLL doctors are going to start testing us for newer prognostic markets (e.g.? NOTCH1).

8 Replies

The late Dr. Hamblin's article is fairly readable...


There have been updates in the literature by Dr. Kostas Stamatopoulos, who is still exploring these genetics...

Mutated is always better as a pool than the unmutated, but there is variation in each group... unmutated is more aggressive and carries a poorer prognosis, based on data from FCR etc, going back 5-10 years.

Things may be changing, but the small molecule data is still thin...

Some CLL research hospital are testing for subclones, perhaps as part of a study, but it has no clinical application yet... I think the next big step will be NGS... likely in 5 years... then subclones will be tested.

Certainly, you can get advanced testing at private labs now, in the U.S., most patients pay out of pocket, but I know a number who have had their insurance pay. CLL specialist seem to know the ins and outs better than the average hemaetologist does, as they make a case as to why the tests are needed.

You should have the VH family at your finger tips... that's what drives your CLL for better or worse.



My insurance paid for sequencing so worth a shot.


What was the name of test? Do you remember the company that did it?


Thank you for the response. I really appreciate it. I will read the article by Dr. Hamblin you reference.


Hi Dale,

I'm Tri 12 UnMutated and my disease is aggressive.

But it seems with CLL there are often people that experience results that are at the extreme end the statistical curves for their own prognostic markers. (The statisticians would caution that the bell curves are broad and overlap significantly).

The research docs are furiously doing regression analysis on the newest data from NGS (Next Generation Sequencing) trying to find the significance of the over 200 genetic anomalies already found in the data that appear to be common among many CLL patients. But the data set is very small, and the cost of testing is high.

There are a few papers from NIH etc. like this one:

And this one from Nature:

Since Dr. Furman did extensive testing on my blood when CGI was developing their newest tests, I often ask about the current hypotheses the industry is pursuing, but there are few really clear "smoking guns" they have identified so far.

The Focus::CLL™ NGS panel assists in the prognosis of CLL/SLL patients. Multiplexed sequencing by synthesis is performed using the MiSeq System (Illumina). This panel includes selected exons of the TP53, NOTCH1, SF3B1, BIRC3, ATM, MYD88, and Card11 genes.



Thank you for the detailed response. I really appreciate it. I am going to read the articles you referenced. Did you see more than one CLL specialist? I saw Dr. Thompson at MD Anderson.


I originally was seeing Dr. Coutre at Stanford, but did not enjoy working with him, so I switched to Dr. Furman at NY Presbyterian (and did a clinical trial with him 2012-2015). Dr. Furman is much more warm and approachable.

I've met Dr. Lamanna at the Niagara Falls CLL conference 2015, and met Dr. Thompson at a Patient Power/ LLS meeting in New York 2016. I believe either of them would also be a good choice.



I was tested in 10/2013 as unmutated , Trisomie 12, CD 38 neg. and Zapp70 50%. I got FCR till 4/2014 and was MRD neg. after 3., 5., and final cycle. Complete remission and MRD neg. Till now excellent blood counts. MRD since about two years around 0,1 and 0,4% stable. Feeling well.


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