Curious if JAK2+ folks here have had there allele burdens checked over time?
If so, how much did they change? over what time period? what course of meds were you on? how have your blood numbers progressed? how have your symptoms progressed?
JAK2 Allele Burden: Curious if JAK2+ folks here... - MPN Voice
JAK2 Allele Burden
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JT_Marlin
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There was a web seminar recently were an mpn specialist says allele burden isnt important
That is interesting- I had not heard that - I presumed the higher it gets the more likely the disease may progress, eg, bone scarring, clots, etc.?
Not sure but I know they def said it isn't important to know x
in reply to Irishgal12
I saw one too. Most presenters provide email addresses so that you can request a copy of their talk. I was in awe of what I heard. I plan to write and get copies of some of the talks that interested me.
Cheers Anna
Why?. In my opinion the allelo burden is important to know because the more higher, the more symtons will you have.
It can progresse or not and you know more about your disease
I would like to know the paper, autor, etc where I can read it.
Thanks
Hi it was a webinar by mpn will try to find it. Apparently they said symptoms dont go by this neither does progression
« The level of JAK2V617F allele burden can be a predictive marker of a response to treatment of PV. An individual approach to each patient, including a detailed study of molecular factors, is the key to successful prevention of complications and ensuring positive outcomes. »
My understaning is that you are correct. The change begins with one or a few genes mutating. If not checked, more will follow suit until you have more mutated genes than normal ones. That, I understand, is when further progression to MF or PV occur. My previous haematologist kept asking me why I wanted to know my own. I later discovered he had never had an ET JAK2+ patient before and was learning as he went along.
I now have been told what it is (or was) and my professor agrees with my understanding of it's significance.
New Zealand has the same attitude, no clinical relevance to disease outcome. It is confusing as some say it increases the risk of thromboses and also symptom burden.
It would be interesting to know if anyone here has noticed anything positive from lowering their allele burden.
I understand that if you are administering a particular drug and your allele burden reduces, there may be a possibility that the mutated genes are wiped out altogether. I believe there have been cases like this when using Pegasys. That is something my previous haematologist actually agreed with me about!
My consultant wouldn’t do test . I to don’t see how it’s not relevant . Must indicate something as wouldn’t do it to begin with surely ?
I had a test for Jak2 when I was diagnosed, and was told it was positive, but have never been told allele burden. Is that a separate test, or do they know from the Jak2 test?
Currently, the allele burden does not appear to have any clinical significance. It serves as additional information about MPNs, and may one day be helpful. For example, I was tested for JAK2 several years before it had clinical significance. It was considered "good information for a later date", which proved to be true!
According to some haems, patients who get a sustained complete molecular remission (undectable allele burden) do not progress to leukemia or myelofibrosis.
Not sure if this helps, but I watched it a couple days ago, to try and better understand.
There is not a concurrence on the role of mutant allele burden and progression of MPN yet. Some consider it more relevant than others. The doc I see at the Johns Hopkins MPN clinic will recheck it, but only when there is evidence of disease progression, not as routine monitoring. There is some research on this topic. (Much more than these two.)
ncbi.nlm.nih.gov/pmc/articl...
ncbi.nlm.nih.gov/pmc/articl...
"Although most of studies were retrospective in nature, the methods for genotyping and the source of cells were used for genotyping different, and notwithstanding the findings were sometimes conflicting, there is enough evidence to suggest that the burden of mutated allele correlates with defined aspects of the phenotype of MPN and major clinical endpoints. " (Vanucchi et al)
There is also the issue of whether the JAK2 mutation is heterozygous (one side of gene) or homozygous (both sides). Short version is homozygous is worse.
journals.plos.org/plosone/a....
There is more on this as well should one care to look.
My own conclusions are that MPNs are complex disorders with more than one factor that drive disease expression. Increasing JAK2 mutant allele burden is likely not a good thing and it makes intuitive sense that it would be linked to disease progression. Having the JAK2 mutation on both sides of the chromosome is likely worse than just having it on one side. Again, that also makes intuitive sense. There are other issues like the non-driver mutations that are linked to disease expression like TP53 and ASXL1. There are likely other factors that are not well understood like the precise location of the mutation on the JAK2 gene and the specific type of mutation that occurs (there is more than one type of gene mutation). There is lot that goes into driving MPN disease expression!
JT - great question! Unfortunately it is a complex issue with no clear answer yet. I hope we will all have better understanding in the future.
For all your questions, it's important to remember that PV is a highly individualized disease and one person's experience isn't likely to predict yours. As we discover more, predictive factors are being isolated but we're at the beginning of that research is my understanding. Our responses to drugs are also highly individualized and as far as I know, we don't know the clinical use of haematologic remissions yet.
Okay, allele burden is not important but many haems are aiming for molecular remission...
« MPN patients treated with JAK2 inhibitors show considerable improvements in blood counts and spleen size, however treatment rarely elicits molecular remission (Deininger et al. 2015) »
What is an allele burden please?
My JAK2 went from ‘indeterminate’ in November 2019 to positive, allele burden 15% in March this year - I gather the plan is to repeat at the end of the year....
Although I'm having some trouble finding it at the moment, I have seen data and charts showing a relationship between the allele burden and the stage of myelofibrosis. I remember it saying that 18%, which was my allele burden upon 1st check was within the range for what they considered stage 1. My bmb showed that I was also mid-late stage 1. My MPN specialist is wanting to check my AB again as he believe it's an indication of how well Pegasys has been working for me. Not making any statements here, just what I've been told and what I've read.
When diagnosed with ET (Feb 2019) I was told I had the JaK2 mutation but not told the allele burden (indeed I only became aware of it and its possible significance through reading on this forum etc). I don't know if I wasn't told because a) it wasn't included in my tests or b) it was included but they didn't want me to know and perhaps worry about it ...
Somewhere on this forum recently, in a thread about possible natural supplements to MPN treatment, I recall reading of a member whose allele burden had gone in a few years from around 80% to 11%! He was having Interferon treatment, I think, and was also taking his own choice of herbal and other natural supplements. Carry on decreasing at that rate and it seems as though the MPN could be "cured" (allele burden reduced to near zero or undetectable level, malignancy totally or almost eliminated?) ... or could it?
I'm only a raw beginner in these matters, on a steep learning curve, but my reading so far suggests that, broadly speaking, a higher allele burden would be associated with disease progression and a worse outlook ... yet it seems that the relationship between allele burden, symptom burden, and prognosis is far from straightforward. There may be significant inherited factors, for instance, meaning that for a given allele burden some people have a better or worse prognosis because of the effects of the genes they were born with, in conjunction with the effects of the burden of acquired mutated genes.
Just now I have been looking at the "Sanger MPN personalised risk calculator". It asks for various information, including mutations where known, but it does not ask for allele burden. This may be because the researchers who created the tool realise that most patients won't know their allele burden, or because they do not consider the allele burden (at diagnosis) to have significant predictive value ...
Thank you for raising this interesting topic!
Update here - my allele burden was 6% last year and 10% now, one year later. Though the hospital switched companies which use different assays so I’m told its a bit like apples and oranges.
Separately I have seen research (possibly one of the links here) that generally shows lower burdens being accompanied by higher number of thrombotic events, while higher burdens have lower events but more tied to bone scarring post-PV MF, etc. This of course makes sense since usually it is those who dont know they have an MPN until they have a thrombosis which then gets them on treatment, hence higher burden having lower probability of these types of events.
I have to believe lower is better particularly if youve been able to reverse course on the burden through drugs, eg pegasys, HU, etc.
Thanks for sharing JT. I'm very interested to learn about the significance of allele burden and have asked this question on this forum as well. You still have low percentage of allele burden. what kind of MPN you have ? how your blood numbers looks and any significant symptoms ?
Jak2+, PV diagnosed early 2020 - im a 41 y/o now; had a myocardial infarction in 2016 likely due to PV, and stroke in 2020 which ultimately led to the detective work to find the PV diagnosis. Ive been on pegasys weekly 45mcg for just over a year now.
Platelets had been up in the 600ish range now down in the mid 200s. Hct also up in the mid-50s before all this, now we keep it below 45 with periodic TPs. Also on baby aspirin twice daily. And due to the heart attack i still take meds for that.
Main symptom I deal with is a slight dizziness - not debilitating and not sure if it is from the stroke or the meds - Generally not many other symptoms- occasional itching post shower, and I tend to wake up with my face, ears, head feeling flushed/hot. But always concerned that another stroke could strike anytime.
Thanks for your response JT. I'm JAK2 positive as well but dont know what type of MPN I have yet. I considered low risk (I'm 48) no previous events and this was caught in yearly blood test. Just checked my JAK2 test and there is section (below) about the sensitivity of the test they performed. Mine was saying says 1 percent, wondering what the sensitivity of your test ? probably you can compare between the two. I'm still in learning phase, Best of luck to you, please stay safe
🙏
Methodology:
Total genomic DNA was extracted and subjected to TaqMan real-time PCR
amplification/detection. Two amplification products per sample were
monitored by real-time PCR using primers/probes specific to JAK2 wild
type (WT) and JAK2 mutant V617F. The ABI7900 Absolute Quantitation
software will compare the patient specimen values to the standard
curves and generate percent values for wild type and mutant type. The
numerical values of Sample Mutant Quantity/(Sample Mutant Quantity+
Sample Wild Type Quantity)X100 is reported as a percentage. In vitro
studies have indicated that this assay has an analytical sensitivity
of 1%.
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