During the visit with the MPN consultant yesterday to organise going on Pegasys, I found out the results of my JAK2 allele burden test: 79% ! I am shocked. Consider that I am practically symptom-free. Not sure how to interpret this and am trying to be very rational and calm, but I must admit that it hit a spot inside me and I feel more worried.
Glad to be starting Pegasys and hoping to be able to stay on it, since I suffer from cutaneous sarcoidosis (an inflammatory condition) and alpha interferon may make it worse. Fingers crossed. If I can be on Pegasys, the plan is to test again for allele burden after at least six months.
The clinician explained that the alternative could be Ruxolitnib which will soon become available in the UK.
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Aldebaran25
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The other interferon option is Besremi, which I believe is available in the UK. There is some evidence that Besremi may be easier to tolerate than Pegasys but not all find that to be so. I did not find any difference between the two medications.
There is at least one member with ~90 % and doing well. It seems many other things also affect our well being. I'm under 14-19% at Dx but often feel no good at all.
Anyway the IFN most likely will cut that down nicely. Rux also has potential to reduce burden too.
Hi EPguy and Aldebaran25, I have PV and when diagnosed a year ago my allele burden was 60%. I don't have symptoms apart from itching (which has been relieved very nicely by Ruxolitnib), and occasional fatigue. From my understanding of all the discussions about interferons on this site, they should actually decrease the allele burden percentage. I am hoping to try Besremi at some point, but my hematologist wants to wait and see more studies before switching over: it was only approved by the FDA here in the U.S. in Nov 2021. Good luck to you, and I hope Pegasys works for you: there has been no talk with me of re-testing for the allele burden percentage, so I may raise that when I next see my hematologist. Helen
I'm actually on Besremi. I'm curious what additional studies your Hem would like to see. It has been in various trials for about 10 years and approved in Eu in 2019. Dr is right that we never have enough data to be certain, same on Rux. There's always new info over time.
There is one point your Dr may be watching, I've posted lot on it as I'm affected: the Ropeg (Besremi) trials used far higher doses than we are seeing in actual practice. Here is a post showing some members' doses and CHR status. You can see how much lower doses are than the trial was. I will post a small update soon with even more low doses.
Apologies, yes I realize I addressed both of you, but only Aldebaran25 is on peg. Thanks for sending through the info on Besremi, not sure exactly what my Dr is waiting for. Maybe as I am still only a year in on Rux, he was just happy that my counts had stabilized nicely for now (as I am too!), but I will bring up Besremi again.
My Dr was leaning to Rux over IFN as we discussed switching from HU. He was involved in some of the Rux studies, so is likely more familiar with it. But he's now good with my choice of Bes. My impression is on average, IFN may be the better option for long term use for its better potential on allele reduction. But there is still uncertainty among some Drs how useful that reduction is.
Try not to worry. If you go on peg or besremi ( don’t know about Ruxolitnib) they should bring alle burden down. Hope you find the best one to suit you and good luck. You are ‘on it ‘ now and things will improve.
In 2019, I was diagnosed with a JAK2 allele burden at 84%. I got only mild symptoms at the time of diagnosis which got even milder over the time. After 3 years on Pegasys, my JAK2 is now below 10%. I’ll have it checked next month.
Thank you all for your comments . I have really appreciated them and I feel much better going forward, much more positive. The start of my new phase is set for next Tuesday and I hope to come back with positive news. All the best to you !
Imagine my surprise when my test came back at 89.9%!!! I didn’t have many symptoms either. I’ve recently started Besremi & looking forward to seeing the results
Add me to the list of people with surprisingly high allele burden and few symptoms. I was diagnosed in 2007 at age 44 (had a BMB back then with no mention of AB). I lived life with few symptoms and phlebotomies every few months. Fast forward to 2022 and age 60 when the Dr said it was time for another BMB in preparation to go on a drug. My allele burden was 88%. It freaked me out, and I’m hoping the Besremi (taking since June 2022) will bring that down and do all the other good things!
You may have seen posts here of Hetero vs Homozygous mutations. At 88% you likely have the latter, since that is the trend at higher VAFs. This is seen in studies to respond comparatively well to IFN, at lower doses than for Hetero, so lets hope for your good progress.
whereas it seems that lower AB should be better, most experts will tell you they don’t yet know the significance yet, I just watched a recent vid by Dr V on Bes and he said just that.
I know of some MPN veterans with high AB doing very well, one expert said to me about 3 years his view (not fact) that those with AB under 50 tend to have a easier ride. I would say until more is known prob wise not to obsess about it. Prob wise to try Peg or Bes if you can tolerate it, it’s likely currently the best of the rather poor selection of drugs we have to chose from, just my personal view and I’m not an expert.
This plot from the study shows clearly the impact of VAF. All these are averages as usual, we're seeing in this thread good outcomes with high VAF.
-One curious detail, the smoking rate in Table 1, is signif lower than current rates in Korea, where the study was presumable done. (19.2%, vs 4% in the study) and much lower than prior levels when the study was done.
This suggests selection bias, or an unlikely inverse correlation to MPN and smoking there.
-Their citations are all quite old, curious if there are no other current VAF effects studies.
-Interesting note on testing methods:
"The JAK2 V617F allele burden was calculated using direct sequencing, ...The sensitivity of direct sequencing is 10-20%" They contrast "real-time quantitative PCR, pyrosequencing, next-generation sequencing, and droplet digital PCR" as being more precise. We've had posts discussing the different testing methods, this lays it out nicely. But even this citation is 2013, which might explain their best case of 1% sensitivity. The Ropeg study went down to 0.01%.
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Thanks for sending through the info on Besremi, not sure exactly what my Dr is waiting for. Maybe as I am still only a year in on Rux, he was just happy that my counts had stabilized nicely for now (as I am too!), but I will bring up Besremi again.
JAK2 Allele Frequency/Burden
Allele burden gone down 
Guidance on % Allele Burden test
Allele Burden
