I went to a CLL specialist and they did IGVH testing. An email informed that I had a new test before the doctor actually called me. I think it is saying that I am not hyper mutated. It reads like this:
"IGVH analysis by sequencing demonstrates a clonal but functionally unproductive rearrangement. This rearrangement constitutes evidence of clonality. However, hypermutation analyses of unproductive rearrangements are not reported. Please correlate clinically."
This sounds like it might be mutated, but not hyper mutated. I thought I had medical knowledge, but this has me a little stumped and obviously a little worried. My absolute lymphocyte counts has been hanging in the 16,000 range for about nine months now. The CLL specialist said he would be shocked if I wasn't hyper mutated given how banal my CLL has been over the last two years. He had blood tests for two years to give me base some of his conclusions. So, am I reading this correctly? Thanks.
Written by
Camaroman
To view profiles and participate in discussions please or .
When your doctor does reach out to you ask if they provide a percentage of mutation. Also, what is it? IGVH1? 3? etc. Can look up what subset you belong to.
‘CLL cells with unmutated IgHV were thought to originate from naïve B lymphocytes, whereas CLL cells with mutated IgHV were thought to arise from B cells that have undergone somatic hypermutation (SHM). ... Thus, the proliferation rate of CLL cells determines the IgHV mutation status and patients' clinical outcome.’
‘It was proposed that CLL is not one disease but two separate entities that arise from B cells at different stages of maturation. Because the genomic arrangement of CLL with unmutated IgHV is similar to that of naïve B cells that undergo somatic recombination, it was postulated that IgHV-unmutated CLL cells arise from naïve, pregerminal center B cells and that CLL cells with mutated IgHV originate from postgerminal center normal B cells that underwent somatic hypermutation (SHM) after antigen recognition.
However, recent data do not support this hypothesis. A retrospective analysis of the survival and progression-free survival of 535 CLL patients treated with chemoimmunotherapy showed that the percent deviation of the immunoglobulin heavy chain gene variable region sequence from the germline sequence (IgHV%) is a continuous variable. CLL patients’ survival correlated with a continuous increase of IgHV% deviation. The higher the percent deviation, the better was the treatment outcome. ‘
My test must not be complete. I have read it ten times and doesn’t answer the questions or use the format I have seen on other reports. There is even some sample reports from the lab available online and it doesn’t read like any of those. So, either the report isn’t complete or there is something that I don’t understand.
What’s the difference, Benefit or no benefits of mutated vs hyper mutated ? I’ve seen a few people refer to them saying there hyper mutated. Please explain thanks John
I would agree ,I have seen a few people refer it to hyper mutated and was thinking there’s another classification but never heard a Dr call it that. Hope you day is going good Lidia. John
When scientists or doctors talk about mutated IGHV (or IGVH), they're using shorthand. I wish they wouldn't do that, because cancer patients are psychologically primed by the word "mutation."
This is not a mutation in the pejorative sense. It's a normal mutation that happens in all B and T cells at particular phases of development. It's what gives us adaptive immunity to ever changing varieties of pathogens. These are the only cells in the body that mutate themselves on purpose during cell development.
The technical term is somatic hypermutation.
Somatic - happens in lines of cells that reproduce by division (cloning).
Hypermutation - also called "recombination" - a series of mutations that happen in B-cell receptors (immunoglobulins) and T-cell receptors. The cells re-arrange a few genes, and then the cell is tested for response to self cells (your own cells) or pathogens. If they fail, they chop out another segment until the cell either dies from not reacting to a pathogen, or is killed by the immune system for reacting to a self cell.
You can slow down the playback speed on this video by clicking the gear icon in Youtube:
Immunology - Antibody Somatic (VDJ) Recombination I
Maybe just let it play, and then vow to either never play it again, or repeat until something sinks in. If the latter, you might like to do the whole series, starting with:
Which says right off in the 2nd sentence, "Immunology is a confusing subject in science."
Way more complicated than I or anyone else born in the 50s - including most scientists - ever expected! VDJ recombination/somatic hypermutation was discovered in 1976 by Susumu Tonegawa, who won a Nobel Prize for it in 1987.
The ERIC guideline says: "State whether the particular IGHV-IGHD-IGHJ gene rearrangement is productive or unproductive. Essential criteria for considering a rearrangement as productive include the utilization of a functional IGHV gene and an in-frame VDJ junction bearing the anchors of the VH CDR3, namely cysteine C104 (2nd-CYS) and tryptophan W118 (J-TRP) (the latter part of the W-G-X-G motif of the J-REGION in VH FR4). For unproductive rearrangements, the underlying reason (for example, out-of-frame junction or stop codon) should be mentioned. Before reporting an unproductive rearrangement as a definitive result in clinical routine, one should take particular attention to carefully review the flow cytometry result for the presence of surface immunoglobulin, as well as the sequence at the nucleotide level and the chromatogram, and make additional attempts on either the same or different starting material using the same or different primer sets to exclude technical flaws during the initial amplification, sequencing or immunoinformatic analytical steps."
As Dried Seaweed states, with regard to IGVH, your doctor should explain the report, and they probably intend to.
Depending on the laboratory, the report may provide mostly raw data that has to be calculated by the recipient who then will produce a specified conclusion. Laboratory jargon more often than not produces confusion even for medical Phd's that are not accredited in the specific field of study, and their initial publication is most often user unfriendly.
As you will see by studying credible in depth research publications, the IGHV relationship to CLL and treatment is not yet fully concluded.
I have been influenced by my hematologist to believe that at this time, the two main points for discussion regarding IGHV mutation statusat the doctor patient level are:
1).Mutated or UnMutated - Defined by a percentage of unmutated cells counted in a specified collection. IGVH mutated or unmutated is not defined by one being diagnosed with cll, rather one is born mutated or unmutated, and status does not change as does FISH.
2). Mutated vs UnMutated - Prognostic measure from clinical trial data showing a favorable or less favorable outcome with specific therapies. The most noted is the unfavorable outcomes for unmutated patients treated with FCR.
I heard from my CLL specialist. He said that my IGVH test was unproductive because it didn't seem to have the mutations that are commonly measured and studied. In other words it could be considered uninformative and no particular followup test would give a different answer. Can't say unmutated or mutated from the test. He believes I am mutated and part of that is an absolute lymphocyte count that has been in the 13-18,000 range for three years. My last ALC actually went down three thousand from two months ago. So more W&W and most likely that will be the case for the next five years or so. Thanks for those that commented.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
ClonoSeq ID Test
Australian current treatment legislation 
My two year on ibrutinib check up
Would someone shed some light on a few questions regarding a continuous drop in ALC and the connection to lymphocyte % means? Thank you! 
Any significance with IgVH testing?
