Hi All,
I was diagnosed 5 years ago PV at age 38 and have been relatively symptom free. Treatment has been aspirin and phlebotomy about once a year. After reading some of the posts, I went back and looked at my BMB and JAK2 from diagnosis and saw that my allele burden was 80%... this seems super high! I'm kinda freaking out... what does this mean? Would it be different now that my numbers are more normal? I am so young and have so many more years to live!
I was diagnosed PV in September with an allele burden of 83 %. This is not a brilliant news but hopefully it should get better in a couple of years with Pegasys. I would strongly recommend you to ask your haem to put you on Pegasys , if you don’t have any contraindications. Bloodletting for PV is only a palliative treatment. Many haems are outraged by this « medieval » approach and I personally agree with them. The good news is that it’s definitely not too late for you to dramatically improve your condition and your allele burden.
Thank you! I have an apt scheduled with Dr. Mesa in TX next week and I am gathering questions... I will definitely ask! I am traveling from Oregon to see him so hoping to get some good info 
Relax! Dr. Mesa is one of best MPN specialists in the world, so you are in very very good hands.
Good luck and I hope it works out well for you.
I actually have had a different experience with phlebotomy/venesection. It has been more effective and has less adverse effects than chemotherapy with hydroxyurea. It turns out I am one of those who is HU-intolerant. That is not to say phlebotomy has no adverse effects. The docs over-phlebotomized me to the point that I am so iron deficient that they can't even measure my ferritin levels. However, being anemic is not as bad as what the HU was doing to me. Going forward, we will be more careful with the phlebotomies and see how it goes.
I have become a very strong believer in the importance of individualized treatment approaches for MPNs. We are all different in how our MPNs manifest, how we respond to treatments, and in what our individual preferences are regarding the benefits/risks with different interventions. I hope for everyone that they find a doc who is knowledgeable about MPN treatment and respectful of the patient's right to choose.
I’ve had a good experience with my 9 venesections during the first 6 weeks of my PV to reduce the hematocrit level, « but conceptually, if you’re thinking what you want to do to cure the disease, getting rid of the mutant clone would make sense», and unfortunately you can’t achieve that with venesection/HU alone.
That is certainly the hope for the future. A true cure - eradicating the mutation would be ideal. Meanwhile, the best we can do is to manage the symptoms. Perhaps a next step will be if the disease progression can be slowed down. Meanwhile, we just all will have to do the best we can do.
Hello. I can't help you bc I'm CALR positive but maybe this article will help you...
Broadly speaking, a JAK2 mutant allele burden of less than 50% is predictive of a lower symptom burden. People with ET tend to have the lowest mutant allele burden, those with MF the highest and PV somewhere in the middle. How genetics play out is more complex than the broad numbers however. There are different types of mutations: base substitutions (transitions and transversions), deletions and insertions. The type of mutation and its location on the genome can affect how the mutation is expressed. Some mutations are silent, other have significant effect.
With PV, the most common type of mutation is a G-transversion. This happens when the nucleotide sequence is changed and the body does not repair it. The four nitrogenous bases in DNA are adenine, and guanine (purines), cytosine and thymine (pyrimidines). Normally a purine binds to a purine (A-G or G-A) or a pyrimidine binds to a pyrimidine (C-T or T-C)
In a G-transversion a purine and pyrimidine bind (G-C or G-T). Depending on the percentage of the mutations and how they are expressed, the symptoms we experience with the JAK2 mutation become evident.
The JAK-STAT pathway is one of the body's kinase systems. It is responsible for many processes including hematopoiesis (blood cell production), production of inflammatory cytokines, tumorigenesis, and apoptosis (cell death - part of healthy body function). Simply put, the JAK2 mutation can cause the JAK-STAT pathway to be overactivated. The "on-switch" is "on" too much. The kinase systems are very complex and the JAK-STAT pathway is only one of these systems, which do interact with each other.
I have JAK2+PV with a mutant allele burden of 25%. I have a relatively indolent form of PV in that while I have thrombocytosis and erythrocytosis, I have never had any incidents of thrombosis and only mild splenomegaly. In fact, I tend more towards hemorrhage and when my platelet levels rise my von Willebrand (clotting) factors tend to drop below normal. I was actually diagnosed with ET over 30 years ago, which progressed to PV about 6 years ago. My own situation is more complex in that I have another kinase-based disorder, Neurofibromatosis type 1. This is a Rasopathy - causes disruption in the RAS-MAPK pathway. As a result, I was diagnosed with a brain tumor in April 2019, a pilocytic astrocytoma that was successfully resected in June 2019. In what may or may not be related, I was just diagnosed with a bone tumor on my mandible. In process of finding out what this is and what to do about it. In what is likely unrelated, in April 2018 I was diagnosed with atrial tachycardia and had a successful heart surgery to deal with that.
The way I explained all of the above is certainly an over-simplification, but is hopefully accurate enough. I hope this helps you understand a bit more. Please know that I am not medical professional. My own background is in clinical psychology. With so much going on in recent years, I have worked to educate myself so I could have a better understanding of what is going on with my own body and have a more informed approach to the decisions I have to make. Please do know that while a mutant allele burden of 80% is concerning, it is not an inevitable death sentence. It is a positive sign that you are relatively symptom free. You will certainly be in good hands when you go to see Dr. Mesa. One of the best things you can do is to consult with a true MPN-expert doc. Most hematologists deal so rarely with MPNs that they really do not have the experience to provide optimal treatment.
Meanwhile - hang in there! Try not to worry too much. Know that lots of us manage MPNs for many years and still have good, long lives despite some challenges. All the best.
I am not sure whether allele burden is predictive of the symptoms burden. I’ve got 83% and no symptom. As far as I know the allele burden is mainly predictive of the evolution of PV into MF. In other words the lower the allele burden the lower the risk of developing MF.
I think you are correct about the mutant allele burden and the progression of the MPN. The research on the role of the JAK2 mutant allele burden and symptom burden is still emerging and there may not be a straight line correlation between allele burden and symptom burden, but there appears to be a broad tendency in that direction. How mutations manifest is quite complex and I doubt there will ever be simple explanations for what we experience.
Great ( and complicated!) information! I suppose the lesson is that we are all different and while there is emerging information about progression and symptom burden, we are all unique and our experiences are all different. I suppose that I am going to continue to try to do the best I can by my body and be super thankful that I am not plagued with symptoms. I go the gym 5 days a week and work and enjoy my family... we have to continue to live and find joy for this diagnosis doesn't define us, nor determine our fate.
Taking good overall care of your body is absolutely the best thing to do. I added the practice of Qigong to my exercise and general care routine. it has really helped with my healing post-surgery and has become an important part of my healthcare and stress management. Also lost 50 pounds in the last year or so (deliberately). Along with the decrease in blood viscosity due to the phlebotomies, my blood pressure returned to normal and I just plain feel better.
Wishing you well in the new year and hoping you find an optimal treatment plan for your own MPN care.
I have been diagnosed recently with ET and in all of my paper work I cannot find an allele burden %. Is that because I am triple negative ET?
Yes. It is often believed that with the triple negative patients that their particular gene mutation has not been discovered yet. Kind of like how CALR wasn't discovered until 2013.
Does cone shaped breast / PECK mean I have something to worry about?
what to think? 
What does the fatigue feel like?
