High Jak2 burden with Tet2 mutation

[Flynn2107]

I was diagnosed with P-vera a few months ago. My bone marrow biopsy showed I have the Jak2 v617f mution at 88% allele burden, this sounds very high to me. I also have a Tet2 mutation at 25% allele burden. Anyone else have high burden like this. My Doctor has down played the 88% burden, but my reading makes me think I will progress to myelofibrosis soon. Any opinion would be appreciated.

[cmc_ufl]

I'm sure others will be of more help with this question, but one thing I would suggest is that you ask your doc about getting on some form of interferon (depending on your location, likely Pegasys or Besremi). These have been shown to reduce the allele burden for many MPN patients.

[Flynn2107 in reply to cmc_ufl]

Thank you so much for your replies to my post. I am closely watching the US FDA approval process for Besremi in the USA. My doctor is only interested in hydroxyurea, I may need to find a doctor that will prescribe the new ropeginterferon when it is approved.

[mhos61]

There is a member with PV (Paul123456), who initially had a high allele burden (can’t remember how high)and also theTet 2 mutation. He has had fantastic results with Pegasys.

Maybe if you look up members on this site you may find his profile.

[Manouche in reply to mhos61]

Paul123456 is indeed the JAK2 champion on this forum: healthunlocked.com/mpnvoice...

[mhos61 in reply to Manouche]

As are you!

[Flynn2107 in reply to mhos61]

Thank you for your reply, Paul123456 is very similiar to my condition. I read all his earlier posts for help.

[hunter5582]

Allele burden is most certainly relevant. There is a significant body of research to support this as well as an emerging consensus that it does matter. Here are just a few references. ncbi.nlm.nih.gov/pmc/articl...

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

ashpublications.org/blood/a...

Non-driver mutations like TET2 also play an important role in symptom burden and risk of progression. There is considerable research ion this as well.

ashpublications.org/blood/a...

ashclinicalnews.org/news/ne...

They key thing to understand is that Allele Burden and Non-driver mutations increase risk, but are not a certainty of a specific outcome. You are correct in thinking that 88% is a fairly high number. Combined with the TET2 mutation it is a valid cause for concern, but it does not meant that you will progress to MF or AML. It speaks to the importance of opting for the most effective treatment intervention with the highest possible chance pf preventing progression of the MPN.

It sounds like you are already aware that PEGylated Interferon is the treatment of choice to prevent disease progression. The studies are quite convincing in this regard. I will not relist those refences as I expect you have already seen them. It is too bad that your current doctor has not. You are absolutely correct in thinking that you need a new doctor if your current doc only wants to consider hydroxyurea. Here is a list of docs with MPN expertise. mpnforum.com/list-hem./ . Do whatever it takes to see on of these MPN Specialist. it is the best way to receive optimal care.

FYI - I also have PV. My MAB is only 26%. I also have a non-driver mutation, NF1. I have been on a phlebotomy-only protocol. I am HU-intolerant , experiencing toxicity even at very low doses. My symptom burden from the PV and the phlebotomy-induced iron deficiency has increased. Therefor, I have opted to begin treatment with Pegasys. I was waiting for Besremi (ropeginterferon) to get approved, but decided not to wait. the plan is to switch to Besremi when it gets approved. We made this decision based on my current symptom burden and increased risk of progression. At age 65, I decided it was time to give this a try to optimize my quality of life and improve my odds for progression-free survival.

I hope you have to opportunity to receive the care you believe to be in your best interests as soon as possible.

[Flynn2107 in reply to hunter5582]

Hunter, thank you so much for your in depth reply, it is very helpful to me. I have seen some of the research you listed and am convinced I need to be on interferon. I asked my doctor about it and he only talked about the flu like side effects patients get. I am hoping the US FDA approves Besremi soon, if not I may need to start on Pegasys. If my doctor doesn't agree on my next visit I will need to find a different hemotologist. I also have a slightly enlarged spleen and the Besremi research studies were only done on patients with normal spleen size. Hope that doesn't prevent me from getting on interferon. My doctor thinks the hydroxyurea treatment can keep my RBC low enough to shrink my spleen and said we will do another ulrasound in Sept to check. Again thank you for your helpful reply and I hope we have good response to our treatments.

[tifftriesit in reply to hunter5582]

Do you experience severe fatigue? I’m not on any medication other than Warfarin and I think I should be to help with my severe lack of energy. Thoughts?

[Flynn2107 in reply to tifftriesit]

I am just now getting over my fatigue. I had five phlobotomys in six weeks and 500 mg HU per day and it drove my HCT from 60% down to 29%. Any lower and I would have needed a transfusion. Doctor took me off the HU and added iron and folic acid supplement to raise my numbers. When my HGB gets back to 13 we will stop the iron/folic acid and go back to the HydroxyUrea to control my numbers. I had severe fatigue and light headed when I stood up symptom when my numbers were so low. My Hgb is back to 10 and I no longer have the fatigue. Low iron and low cbc numbers caused my fatigue. Hope you get your stamina back.

[hunter5582 in reply to tifftriesit]

I have also had mild fatigue as a result o0f the iron deficiency, but never directly from the PV. I expect this will get better once the Pegasys is controlling my erythrocytosis and we can get my iron levels higher.

[Manouche]

Hi Flynn, my Jak2 AB was about the same as yours at diagnosis : 84% (83.8). After the first 11 months on Pegasys 45-90-135mcg, it’s now down to 50 (49.9 %). It’s interesting to note that some patients who were diagnosed with a 100% jak2 AB still managed to get a full molecular remission with weekly interferon. So yes it’s not a great news to have a high AB but it’s definitely not an irreversible process.

[Flynn2107 in reply to Manouche]

Thank you for your reply, its very helpful and hopeful to hear from someone with similar condition. I hope I can get on interferon soon and have some remission like you have.

[Ben2022]

I also have high burden of JAK2(79%)and TET2(39%), but my doctor said TET2 is not risky and will not progress to MF soon. SRSF2 mutation is only risk factors for Pv in MIPSS score system. Hope to discuss with you.