Zap-70 down but not out?

[Guest guest]

I don't count Zap-70 out completely. Recent work being done in Dr. Byrd's back

yard at OSU ( Zhang et al.) have found a gene array (L2RB, CD8A, CD247, LAG3 and

KLRK1) which accurately predicts IgVH mutation status. These genes are part of

the Zap70 co-expression network.

They state " We have identified a set of genes that are potential CLL prognostic

biomarkers IL2RB, CD8A, CD247, LAG3 and KLRK1, which can predict CLL patient

IgVH mutational status with high accuracies. Their prognostic capabilities were

cross-validated by applying these biomarker candidates to classify patients into

different outcome groups using a CLL microarray datasets with clinical

information. "

http://www.biomedcentral.com/content/pdf/1471-2105-11-S9-S5.pdf

So maybe this will get some traction in the future...

~chris

[Guest guest]

I am going to reiterate what I have repeatedly mention, and I apologize to

everyone for being redundant. I believe that it is very important to remember

that:

Prognostic factors are only of use in predicting how a population of patients

will fare.

Please remember this. These prognostic factors are of great interest to

physicians as we try to learn more about CLL, but there is no tool more useful

for taking care of patients than one developed in 1975 (Yes, 1975) called the

Rai Stage. Dr. Rai's work not only gives physicians an indication of how to

determine who are progressing, but when treatment should be initiated.

Regarding zap-70, it does seem that zap-70 is the most important prognostic

factor, and can trump the others when they are discordant. (Mutated and zap-70

positive is worse than unmutated and zap-70 negative.) This is an important

idea for us as it suggests that inhibitors of B cell receptor signaling are

potentially going to be very effective, such as PCI-32765.

I do recommend not letting the prognostic factors drive anxiety. Right now, we

do not use them for any treatment planning. This will likely change in the

future, but for now, we have no data that it should change anything.

Rick Furman, MD

>

> I don't count Zap-70 out completely. Recent work being done in Dr. Byrd's back

yard at OSU ( Zhang et al.) have found a gene array (L2RB, CD8A, CD247, LAG3 and

KLRK1) which accurately predicts IgVH mutation status. These genes are part of

the Zap70 co-expression network.

>

> They state " We have identified a set of genes that are potential CLL

prognostic biomarkers IL2RB, CD8A, CD247, LAG3 and KLRK1, which can predict CLL

patient IgVH mutational status with high accuracies. Their prognostic

capabilities were cross-validated by applying these biomarker candidates to

classify patients into different outcome groups using a CLL microarray datasets

with clinical information. "

>

> http://www.biomedcentral.com/content/pdf/1471-2105-11-S9-S5.pdf

>

> So maybe this will get some traction in the future...

>

> ~chris

>

[Guest guest]

There is one study from Rassenti which finds that ZAP-70 adds

significantly to IGHV mutations. The method used employed a different antibody

than the original studies (which showed a high concordance with IGHV

mutational status) and rather than being an indirect double layer flow assay,

used

direct labelling single layer flow. Several commercial labs have attempted

to set up the same assay, but I have not been convinced that these assays

have been useful. While I have the highest respect for Tom Kipps and

Rassenti, my own lab have found all ZAP-70 assays unreliable, with extreme

variability from day to day and even from hour to hour. There is still an

ongoing international workshop trying to standardize ZAP-70 assays, but we

have stopped reporting the answers.

Terry Hamblin

I have heard that Byrd has been similarly disappointed. So a search

for a surrogate for IGHV mutations goes on.

In a message dated 22/11/2010 14:00:36 GMT Standard Time,

jfullen@... writes:

Good Morning,

I'm a 77 yr. old male recently diagnosed with CLL. My report states the

following results:

Unmutated IgH gene (Unfavorable prognosis)

Tumor cells are kappa light chain restricted, 50% of white cells (?) don't

understand this result.

Low ZAP-70 (Favorable prognosis).

Lack of classical prolymphocytes, some smudge cells.

Platelets mildly decreased.

Normal male karyotype (?)

Del (11q) Unfavorable.

CD38 80% (Unfavorable)

B2M 2.5, H

These are just some of the numbers. Still have BM report to study. So far

looks like a mixture of favorable and unfavorable results. But for sure, I

have CLL (along with Diabetes). Watch and Wait for now (and STUDY).

I'm really glad I found this site!

Herman

[Guest guest]

Good Morning,

I'm a 77 yr. old male recently diagnosed with CLL. My report states the

following results:

Unmutated IgH gene (Unfavorable prognosis)

Tumor cells are kappa light chain restricted, 50% of white cells (?) don't

understand this result.

Low ZAP-70 (Favorable prognosis).

Lack of classical prolymphocytes, some smudge cells.

Platelets mildly decreased.

Normal male karyotype (?)

Del (11q) Unfavorable.

CD38 80% (Unfavorable)

B2M 2.5, H

These are just some of the numbers. Still have BM report to study. So far looks

like a mixture of favorable and unfavorable results. But for sure, I have CLL

(along with Diabetes). Watch and Wait for now (and STUDY).

I'm really glad I found this site!

Herman

[Guest guest]

You failed to mention the Binet system which is some instances, perhaps for SLL

patients, may give better staging than Rai. The Binet system is used in Europe

and the UK and since this forum is international, it should be included, IMHO.

Still the best marker in CLL is probably Lymphocyte Doubling Time (LDT)

For a quick overview of the Rai and Binet staging systems:

http://www.oncologychannel.com/leukemias/staging.shtml

~chris

>

> I am going to reiterate what I have repeatedly mention, and I apologize to

everyone for being redundant. I believe that it is very important to remember

that:

>

> Prognostic factors are only of use in predicting how a population of patients

will fare.

>

>