MPN Diagnosis: Understanding Key Tests to Overcome Barriers to Care

Lisa Hatfield:

Let’s start where every MPN journey begins with getting the right diagnosis. One barrier patients may face is receiving an MPN diagnosis without fully understanding what testing established it, or whether that diagnosis may need to be revisited over time.

Dr. Abu-Zeinah, what tests and clinical information are typically used to confirm an MPN diagnosis, and what should patients understand about their specific diagnosis from the beginning?

Dr. Ghaith Abu-Zeinah:

I think this is a topic that is the focus of, really, my clinical practice, and I want to start first by introducing what MPN really means. So, having an MPN, it’s a myeloproliferative neoplasms. When we talk about MPNs, I think I’d like to kind of break that barrier first by pointing out that MPNs are blood cancers.

I think that certainly can create a bit of a sense of fear about having a cancer diagnosis. There’s obviously stigma around the word cancer, but it’s very important that patients are aware and educated of what it is and how it’s diagnosed. So MPN again stands for myeloproliferative neoplasms.

And that is really the broad term that’s used to describe three main diagnostic subtypes, essential thrombocythemia, or ET, polycythemia vera, or PV, and myelofibrosis, or MF.

So, when it comes to the MPNs, what’s common across these three subtypes is the type of gene mutation that is acquired, not inherited, but acquired, that leads to the abnormal development of blood cells. So it really comes down to identifying an abnormality in blood cells, typically with your primary care physician on an annual physical, or if there are symptoms that prompted testing, that’s number one in the criteria, is identifying abnormal blood counts.

Coupled with the presence of a mutation, what we call a driver mutation for MPNs. And it’s generally one of three mutations, or three genes that are mutated. And those are the JAK2, the CALR, or C-A-L-R, and the MPL, or MPL gene.

But there is about a 10 percent of ET and MF that is triple-negative, or negative for these three mutations, and might have a mutation in a different gene that requires, really, an extended panel of gene tests. We call that a myeloid NGS, or next-generation sequencing.

So we start off with blood counts, gene mutation testing, and of course, we take the clinical presentation into account. What are the symptoms involved? Do the symptoms correlate with what we would expect with one of these conditions, or could there be something else going on?

And once we have established that these two criteria of blood counts and, you know, driver mutation are positive, the third major criterion required to establish the MPN diagnosis is findings on the bone marrow biopsy.

So as a blood cancer, it really originates from the bone marrow, and for us to know exactly what subtype we’re dealing with, we really have to confirm that the presence of the MPN in the bone marrow and determine which type it is. So that would be the third element for the three major criteria.

There are some minor criterion that help you distinguish one from the other, so when we get to the nuances of, do I have ET or do I have PV? Certainly we know that blood counts are a big distinguishing factor, but there are some minor criteria. For instance, what is your EPO level? EPO, erythropoietin.

That can be very low in some patients with PV, but it’s not expected to be low with ET or myelofibrosis. Similarly, there are other blood tests. For instance, lactate dehydrogenase is a minor criterion in distinguishing myelofibrosis, perhaps, from ET. It can also be elevated in PV.

But really, if you’re going to remember anything out of this, I guess my [ACT]IVATION tip is to get an MPN diagnosis, you need to look at blood counts, presence of a driver mutation, and the bone marrow biopsy findings, and couple that with the clinical presentation.