IVGH mutation status

[CLLmoxie]

Can a CLL patient go from unmutated to mutated? That appears to be what my recent test indicates. My appointment is on 6/4.

[Newdawn Administrator]

It’s my understanding that the IgHV status remains constant and doesn’t change or evolve like chromosomal deletions. Is it possible the result was initially inaccurate?

Newdawn

[CLLmoxie in reply to Newdawn]

Possibly since unmutated was at hem-onc and mutated was at CLL specialist.

[Newdawn Administrator in reply to CLLmoxie]

This article suggests the possibility however for the speculative reasons given in the conclusion;

clinical-lymphoma-myeloma-l...

Conclusion

‘The existence of these new nonplausible heavy-chain variable regions suggests either the CLL cancer stem-cell maintains the ability to rearrange a previously silenced IgH allele or more likely that the cancer stem-cell produced at least 2 subclones, suggesting that the CLL cancer stem cell exists before the process of allelic exclusion occurs.’

It’s complicated testing and mine has failed twice now!

Newdawn

[CLLmoxie in reply to Newdawn]

My doctor answers email or MyChart questions fairly quickly - I will let you know what he says.

[Smakwater in reply to Newdawn]

In compliment to your citation, mutation status results are based on counting which involves equipment and observation that are subject to calibration and interpretation.

The range for qualifying is respectively ≥2% = mutated, <2% = unmutated. However the publishing listed below states, "For example, concurrent ZAP70 overexpression or 11q deletion by FISH are more likely to be associated with unmutated disease".

ncbi.nlm.nih.gov/pmc/articl...

Therefore if the measure is borderline, a high risk patient may receive differing results depending on the physicians interpretation.

JM

[CLLmoxie in reply to Smakwater]

I was told ZAP70 is no longer considered reliable.

[Smakwater in reply to CLLmoxie]

However, there are equivalent measures, e.g., TP53 or considered high risk karyotypes.

[johnl]

Mine actually went the other way, from mutated to unmutated. the latest Dr attributed it to a faulty first test, however my 16.5 year wait and watch sure looked like a mutated IGHV patient.

john

[CLLmoxie in reply to johnl]

We will take whatever good results or outcomes we get 😊 I have probably had CLL for over ten years and only known for about it for one year of W & W with treatment soon.

[Annvaughan]

When my husband was first tested locally for mutation status it came back mutated. Then we went to Mayo for a second opinion and the test came back unmutated. My husband joined the NIH Historical study and they retested since there was a discrepancy between the two tests. The results came back and indicated 2% unmutated. He is right on the borderline between mutated and unmutated.

[CLLmoxie in reply to Annvaughan]

Mine this time was 6% mutated

[placebo_09]

Most tests like this have a margin of error usually indicated by a percentage ( + or - x%). My first IVGH test, that said I was mutated, was probably within the margin of error because the result was right on the cut-off for being Mutated. A second test was done by different lab as part of a clinical trial clearly put me in the unmutated category.

[SethB34]

I was tested as unmutated with a rate of .68, well below the 2 pct threshold. So I'm going to have to keep a closer watch on it. I wouldn't be surprised at all if reports come out in the future stating that mutation status is not so constant after all. One question I have is regarding the rate of mutation. Has anyone had experience, mutated or unmuated, with having rates of mutation go up or down?