JAK2 mutation = MPN????

[ERei]

I am totally confused by an article I read in the MPN Research Foundation’s Spring newsletter & was hoping someone could clarify. The article stated:

“It is known that JAK2 mutations are found in 'healthy' people around the world, particularly in older individuals. Most of them don’t acquire characteristics of MPN’s. The question is why do some ppl with the mutation develop an MPN while others don’t”

Doesn’t everyone who has the JAK2 mutation have an MPN?

If not, how do you know which people with a JAK2 mutation have an MPN and who doesn't?

[hunter5582]

Not everyone with a JAK2 mutation develops a MPN. Even among those who develop a MPN, many actually acquire the JAK2 mutation in early childhood. It can take decades for the MPN to manifest. Some never develop into a MPN but do develop Clonal Hematopoiesis of Indeterminate Potential (CHIP). The understanding of CHIP is growing as well as an understanding that there can be complications due to CHIP even without a MPN developing.

[EPguy]

You're reading about "Clonal Hematopoiesis of Indeterminate Potential".(CHIP)

This is an older report that is not directed specifically to MPN (rather "hematologic neoplasia") but the plots are illuminating, including increase in CHIP with age.

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

"CHIP shows a clear association with age." The plot in this report shows all the mutations they found, but these pts don't have hematologic neoplasia. Note that many what we call "non-driver" (not Jak2 in this case) were found.

This plot shows up to ~12% Jak2 without symptoms. Currently Jak2 can be detected down to ~0.01%. At these levels even more healthy older people are likely to be found.

--

"...how do you know which people with a JAK2 mutation have an MPN and who doesn't?"

We get our MPN Dx by factors beyond mutation level.

Table 1 in this report shows one common set of criteria for PV and ET. Note that more than Jak2 is required. (and/or CALR/MPN with ET)

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

CHIP

[Proton_1]

Interesting post and replies.

In the example where the JAK2 mutation occurs early in life but the MPN doesn't present until decades later:

I've read about two different ways this occurs (or at least this is how I interpret what I read), but I don't know which is correct. Does anyone know if either is correct or partially correct? The first explanation is that the JAK2 mutation that is acquired early in life triggers slow clonal expansion that eventually results in an MPN diagnosis (due to exponential growth) later in life when the effects are observable, in other words, when the phenotype of the disease can be determined. For example, in ET, platelet counts eventually start trending upward and exceed the upper limit, changes in bone marrow can often be seen, and symptoms may be present. The second explanation is that the JAK2 mutation acquired early in life doesn't result in expansion of the clone, but something later in life triggers the expansion.

Any thoughts?

[hunter5582 in reply to Proton_1]

I do not think anyone is totally sure about what triggers the MPN to manifest after the JAK2 mutation is acquired. There are several viable theories as you have outlined. It seems likely that there are multiple factors involved as well as multiple pathways to manifestation of a MPN. Hopefully we will learn more over time.

[ERei in reply to hunter5582]

If normal healthy ppl can have the JAK2 mutation & not have an MPN, maybe being JAK2+ is not really unhealthy & should not be part of the diagnostic criteria for having an MPN?

[ainslie]

good questions, if you ask the expert experts they will say we don’t know why some with Jak 2 do get MPN and some don’t. If I remember those who don’t may have lower levels of Jak 2 but was just a possibility not a fact.

Usually people with MPN find out they have it by symptoms or routine blood test if they are lucky , the unlucky ones only find out after a clot or stroke. In my case I started with itching and vertigo , it took 2 years and seeing many docs before some one said you look very red and bulging veins, they did a cbc and Hgb was 197 and Hct 56 , then I got a Jak 2 result.