Variants
About 6-7 weeks ago I transferred from my local hematologist to an MPN specialist - a move I feel really good about. She has done some different lab work and another BMB and changed my diagnosis from ET to Prefibrotic MF. I am JAK2+. She also had the lab folks look for other variants and they also found DNMT3A and TET2. Does anyone know if that is normal to find them with JAK2?
Congratulations on making the change to a MPN Specialist. this will give you the opportunity for improved quality of care, optimized for your unique MPN profile.
DNAMT3A = DNA methyltransferase 3 alpha gene. TET2 = Ten Eleven translocation 2 gene . Both are involved in functions that include DNA methylation. Both are involved in cancers.
DNMT3A and TET2 are two of the known non-driver mutations that can affect how a MPN presents. "DNMT3A is the next most frequently mutated gene in MPN after TET2, affecting 7–10% of patients." ncbi.nlm.nih.gov/pmc/articl...
The short and oversimplified explanation is that the presence of these non-driver mutations can influence risk of progression of the MPN. As you can see from the attached diagram, the action of these genes is quite complex. Short of gaining an advanced degree in molecular biology, the best way to understand would be to ask your MPN Specialist for an explanation of what these mutations mean in your case.
Like you, I have an additional mutation. I have both the JAK2v617f mutation as well as the NF1 mutation. In my case, the NF1 mutation is germline, which causes another condition - Neurofibromatosis Type 1. This is what caused the brain tumor I had resected 4.5 years ago. The NF1 mutation increases my risk of progression into AML, but it is not known to what degree.
What I find is that it does not pay to worry and fret about what it means to have an additional mutation. It is not something I can change. I focus on the things that I can change that can make a meaningful difference in my chances for successfully managing the MPN. I chose Besremi as an option that may increase my chances of progression-free survival. I limit my exposure to carcinogens, mutagens, and other toxins that might promote progression or risk of secondary cancers. I eat a healthy diet and work to live a healthy lifestyle. I try to follow the credo of the Serenity Prayer - Serenity to accept the things I cannot change, Courage to change the things I can, Wisdom to know the difference.
Here is some information if you want to start to do a deep dive on your own. Note that this is some fairly heavy science. Lots of secondary reading needed if you do not have a strong background in molecular biology and proteomics.
medlineplus.gov/genetics/ge...
cureus.com/articles/68356-j...
ncbi.nlm.nih.gov/pmc/articl...
ashpublications.org/ashclin...
I have to say, I don’t quite know how to say thank you for a response that is this heartfelt. Your willingness to share this much is appreciated more than you will know. Your response helps me understand some of the technical aspects of my condition, but knowing there are people out there that will share like this is at least as valuable. Thank you so much!
Hi! I'm stainedbrightly from Reddit and I'm so glad you found the forums!
I see Hunter has already jumped in, so I'm glad someone could answer your question more thoroughly than I could.
I agree with Hunter about trying not to worry about what cannot be controlled in our bodies. Secondary mutations are common with us and science doesn't always know to what degree they impact MPNs.
There is one report with reassuring finding on these:
"With regards to fibrotic progression, no association with the CHIP-associated mutations TET2, ASXL1, DNMT3A was found". It's discussed in this post:
healthunlocked.com/mpnvoice...
As usual one study is not a final answer but does add to what we know. Some other reports do show an influence with ASXL1.
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This is another post where I discussed results of an interferon trial that addressed these mutations and other things. It's not easy reading since the report also wasn't. But if you're interested:
Very good stuff! Thank you. A fair amount of it went over my head, but what I understand made me feel better.
Hi!Yes, over time, one can acquire other somatic mutations on top of the driver mutation JAK2V617F.
I also have JAK2 and DNMT3A. My hematologist said that the DNMT3 is not of high significance. That’s all I was told. Good luck!
Hi, I have ET and a TET2 mutation , I was told that about10% of the elderly population have this mutation so 'not to worry about it'. So I don't worry about it but I did feel about hurt being referred to as elderly!!!
Hahahaha! I understand! Thanks
Very similar as my initial ET is more likely pre-PMF but as it doesn’t change treatment plan not worrying about it. I too am Jak2+ and have the TET2 mutation as well.
My MPN specialist basically said the fewer mutations the better 3-) but the science is still out on how exactly these particular mutations might effect chance of progression. So will keep keeping on, take Peg and try to continue other positive lifestyle changes.
It’s great you are now with an MPN specialist. These are rare conditions (and pre-PMF as a separate diagnosis even more rare and recent) so best to be under the care of experts - it really has made such a difference for me personally.
one thing that may be of interest is that these “extra” mutations can be either acquired or something you’re born with and acc to my doc it’s the acquired ones that may mean something for MPN…
Ferments (kefir, komucha, fermented veges)
Switched from Hydroxyurea to Pegylated Interferon (PEGASYS)
RE: 28F, Terrified I might have PV
Besremi to the Rescue 🤞🏼
Does being jak2 negative pretty much rule out mpn?
