11 Q deletion? Mutated or unmutated?

[kathymac52]

I asked our CLL doctor if my husband with 11 q deletion was unmutated which is what I had assumed, but he said he was mutated. I am confused. He also tested positive for ZAP 70. I got his FISH results, but that did not clear this up. Help??

[AussieNeil Partner Administrator]

That's great news for you and your husband. While there's a good chance that someone ZAP-70 positive has unmutated IGHV CLL, (particularly if they are also CD38 negative from the Flow Cytometry test) it's only a correlation for the definitive (and much more difficult) IGHV test.

Neil

[Newdawn Administrator]

The FISH test in itself doesn’t establish the mutational status Kathy as Neil indicates in his reply. That requires a separate testing process. The mutational status can’t be definitively guessed on the basis of the FISH result.

This link explains;

ajmc.com/insights/personali...

The information in this link explains how percentage of CD38 can indicate (with 70% accuracy), the mutational status from the flow cytometry test. Expression under 30% is indicative of a mutated status and a more favourable prognosis. The link (and my post explains ZAP 70).

There is always the possibility your haematologist has this IGHV information on your husband from the initial flow cytometry test.

healthunlocked.com/cllsuppo...

Best wishes,

Newdawn

[DebKat999 in reply to Newdawn]

A question if I may just to help clarify this for me - does this information mean until you know what percentages of ZAP70 and CD38 you are (I am positive for both, but dont know yet my percentage for either) you shouldn't assume that you are unmutated only because you are indeed positive for both?

[Newdawn Administrator in reply to DebKat999]

That’s right DebKat. It’s the percentage which is the key factor as explained in the link.

If the testing has been done and percentages established, it may be that the specialist then confidently uses the expression ‘unmutated’ based on the results.

This is the explanatory link;

‘Patients with less than 30 percent CD38+ B-CLL cells are likely to have a favorable clinical course requiring minimal or no therapy. Patients with equal to or greater than 30 percent CD38+ B-CLL cells are more likely to have an unfavorable clinical course requiring earlier and ongoing treatment. Significant differences in survival are also thought to exist between these two groups. CD38 expression remains stable over time in the majority of patients, but it is known to change in approximately 25 percent of cases. Its level of expression does not seem to be influenced by chemotherapy.

The connection between CD38 expression and IgVH gene mutational status is not well understood. It appears that patients with less that 30 percent CD38+ B-CLL cells are likely to have mutated IgVH genes while patients with greater than 30 percent+ B-CLL cells are more likely to have unmutated IgVH genes. While this is often the case, there is approximately a 30 percent discordance between assays for CD38 and IgVH mutational status.

Both CD38 and IgVH gene mutation are thought to be useful prognostic indicators in B-CLL, but because of the relative ease of testing for CD38, it is a much more convenient test.

CD38 and IgVH mutational status are just two of a number of prognostic indicators in CLL. Others include, circulating levels of beta-2-microglobulin and soluble CD23, lymphocyte doubling time, serum thymidine kinase levels, bone marrow histology, and chromosome abnormalities.

What is the significance of ZAP-70 in CLL?

ZAP-70 is an abbreviation for Zeta-chain-associated protein kinase 70. This protein is a member of the protein-tyrosine kinase family and when expressed on B-CLL cells is surrogate marker for IgVH gene mutational status. The presence of ZAP-70 can be detected by flow-cytometric analysis, and the level of expression is thought to correlate with mutational status.

CLL patients with less than 20 percent ZAP-70 positive B-CLL cells are likely to have mutated immunoglobulin V genes, predictive of a more favorable clinical course, while patients with greater than 20 percent positive B-CLL cells are likely to have unmutated immunoglobulin V genes, predictive of a less favorable clinical course.'

Regards,

Newdawn

[DebKat999 in reply to Newdawn]

Thank you so much Newdawn for confirming, and for providing this information.

[CaCo82 in reply to Newdawn]

My husband’s flow cytometry showed dim moderate CD-38, but didn’t list an actual percentage. He was negative for ZAP 70. Does anyone know what % dim-moderate indicates?

[kathymac52 in reply to Newdawn]

Dawn, I have his Flow Cytometry. It does say in the comments that the " level of ZAP 70 immunoreactivity (~38%) by CD19/CD5 co-expressing cells is considered positive for this antigen(>20%). However, this result should only be interpreted in the context of clinical, histologic and Immunophenotypic findings diagnostic of CLL/SLL" I might not have all of the paperwork on this??

I could not decipher the FLOW Differential graph..

On his FISH study it appears that Deletion 11q (ATM) showed a percentage of 24.5 with the Cut-off at 7.5 and therefore it was detected. Nothing else was detected at this initial test 3 years ago. This was fro his bone marrow biopsy.

My husband is on Ibrutinib as the second course of treatment as BR failed. He is currently doing well. I just wanted to have as much information as possible. Any other analysis is certainly welcome!

[Newdawn Administrator in reply to kathymac52]

I think you need to clarify this further with his CLL specialist Kathy because it’s an incomplete picture as you say in terms of data and I’d be loathe to speculate. As others have confirmed, this data taken from the flow cytometry test has a 30% inaccuracy rate.

I think the important factor is your husband now being on Ibrutinib and responding well to this particular treatment. The prognostic information can be important in leading us to the right therapy and it certainly sounds as if your husband has now found his.

Hope things continue to progress well.

Newdawn

[Hidden]

Kathy,

The FISH shows the Chromosome involved (11q, T12, 13Q, 17p) and the Flow Cytometry shows the CD38/ZAP70 expression. With ZAP70 + and CD38 - you should ask for the IGHV test to check actual mutation status. It is more likely to be mutated, than not...but still there is some question.

Expression of ZAP70/CD38 is used as a proxy for mutational status....and can be wrong (about 25% +/-of the time). It is not a definite test.....just an indication of "probably"

Scott

[kathymac52 in reply to Hidden]

Thanks Scott, don't know if he had the IGHV test to check actual mutation status. I will ask when we see the doctor in 2 weeks.

[lankisterguy Volunteer]

I am Zap-70 neg but CD-38 Positive and confirmed as UnMutated. My CLL grows at a very fast rate. My first progression (TTFT) lasted 2 years, my most recent was 6 months.

Rather than focusing on the mutation status I believe you can learn far more useful information by tracking the "tempo" of your own disease. Dr. Lamanna uses that to describe her prognostic method.

Observing / tracking/ charting the rise of your ALC and/or growth of palpable nodes gives a better "wind sock" like prediction of how fast your disease is heading for treatment. It's not perfect but it is a guide.

Len

[kathymac52 in reply to lankisterguy]

Thank you! Great advice....so new to this all, so every bit of advice is helpful