What Is ZAP-70?

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What is ZAP-70 (70-kDa zeta-associated protein), and what can it reveal about a CLL patient’s prognosis? Experts Drs. Nitin Jain, Alessandra Ferrajoli and Javier Munoz explore this prognostic marker and what role—if any—it plays in determining a treatment path.   

Sponsored by the Patient Empowerment Network, which received educational grants from AbbVie and Genentech. 

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Transcript

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

Audience Member:

Okay. So we heard a few years ago even, Dr. Jain, I don’t know if you want to—ZAP-70, Dr. Kipps used to talk about it all the time.  Where are we? 

Dr. Jain:                 

So ZAP-70 is one of several prognostic markers for patients with CLL.  So in the morning session, we talked about FISH panel for CLL, deletion 17P.  Then we talked briefly about mutated styles for IGV8 gene where you could be unmutated or mutated.  ZAP-70, CV38, CD49D are other prognostic markers for patients with CLL.  So ZAP-70 is a marker on the surface of the CLL cells. And if you have high ZAP-70, then it is thought to be a poor prognostic marker, meaning that your time to first treatment, if you are on the watch-and-wait approach, if you have high ZAP-70, it’s likely going to be lower.  But again, it’s not just ZAP-70 in itself. 

I think when you look at a prognostic marker, you have to look at the entire picture together.  So patients who are ZAP-70-positive tend to be unmutated for the V gene, meaning that they are high-risk.  They could also be more likely to have deletion 17p or 11q.  So when I look at a patient, and let’s suppose their ZAP-70 is high, it’s positive, but they have other favorable risk markers. So I don’t always know that for sure that if you have just one marker, which is bad, is that like a bad thing to the patient. So I think in my practice, and I tend to look more at the FISH and the mutation status more as stronger predictive markers than ZAP-70 and CD38.

Andrew Schorr:                  

I’ve been at this 19 years.  My first program in CLL was when I was diagnosed 19 years ago. And one of the great, I shouldn’t say old men, senior hematologists in the world is Dr. Kanti Rai—a great mentor for many people.  

And so over the years, I talked to him. And as these different understandings, ZAP-70, all the different things that we’ve been talking about, all the alphabet soup, I said, “Dr. Rye, it sounds like you have a lot of furniture in the room now, and you’re trying to figure out how to arrange the furniture and for which patient.” And am I right, Dr. Ferrajoli?  Is it really you have all these different properties of CLL you understand, and a lot of what you’re doing in research is trying to find out what’s significant for which patient when? Am I right?

Dr. Ferrajoli:       

Yes. So what I tell my patients when they come, and we do this entire battery of tests, big number of tests, is that I’m going to try to give you a report card. And the report card is going to help me in deciding how closely I need to watch you.  So in this case, having a ZAP-70 positivity, it will be like an A- instead of having other characteristics that are associated with more of the smoldering cases is an A+.

So it’s a way to get to know the patients better and anticipate. A lot of being a physician is anticipate and predict what is going to happen. And all of this information helps us.

Andrew Schorr:                  

Okay. So, Dr. Munoz, I know you have people who come in, and they have a bunch of stuff they printed out from the Internet, maybe some stuff from Patient Power or less credible source sometimes. And they come in, and they are in a tizzy on different properties that they think may or are not sure apply to them. And it could be crazy making. I imagine sometimes you have to say let me handle it a little bit. You have to calm them down. 

Dr. Munoz:          

So ZAP-70, for example, another soup of letters, as you were saying, another acronym.

But it’s just one variable. ZAP-70 does not define you. The number of your white blood cell count does not define you.  We do not treat numbers. We treat human beings as a whole.  So we put together all of those variables. And then we make decisions for moving forward as a team.  Medicine is not black or white. I know a lot of patients come to us printing stuff from the Internet, and they want a clear-cut white or black answer. But in reality, medicine, just like life, is more in the gray zone. So you guys, at the end of the day, will listen to many of our options. And you will be in the driving seat.

Perhaps your caregiver will be the co-pilot, and we will be in the back seat, maybe even on the street giving you some directions. But you will be in the driving seat when it comes to decisions.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

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Page last updated on August 13, 2015