Going over my medical records just realized that the MPN specialist ordered a full NGS panel when he did the BMB - I had thought we had just determined the Jak2 allele burden. Turns out that my Jak2 allele burden is 40% - which is high for ET - everything I have been able to find indicates that the average allele burden (Jak2) for ET from a BMB is about 22-26%. At the same time, I have have a mutation at TET2 - only 4% allele burden. My MPN specialist said it was borderline to even report the TET2 number as the local lab has a 2% cut-off for significance.
I asked my specialist what might it mean that my Jak2 allele burden is higher than normal for ET (and closer to the PMF/MF level) and that I also have the TET2 mutation (albeit at a very low burden level). He said in general, fewer mutations better (obviously would not even want Jak2) and lower burden better, but beyond that the science is still out. He did indicate that there are a number of recent studies on level of allele burden in the various MPNs and do they portend to clinical manifestations of MPNs; possible progression and can the allele levels be used as a tertiary diagnostic tool (especially trying to differentiate at diagnosis between ET and prefibrotic MF).
He said the best news about MPNs being re-classified as cancers was that the amount of research and research dollars has exploded over the past few years. He is confident that we will start to see additional therapies and more individualization in the coming years (as we already have started seeing). He also said that if all MPN patients were offered full NGS panels as part of the diagnostic intake, that we would likely find many had more than one mutation. The primary rationale now for not being standard of care is cost and applicability (which is somewhat a circular argument as we don't have enough data on the significance of a lot of the data we would collect from broad application of NGS panels so we don't know if they are really necessary - of course if we had more data perhaps we could draw more definitive conclusions which might impact standard of care...)
After speaking with him, I did come across some interesting studies on level of allele burden as well as sequencing of mutations (does it matter if you acquire the Jak2 mutation or the TET2 mutation first - spoiler alert - it apparently does for clinical manifestation and potentially treatment.
Here are some of the studies:
onlinelibrary.wiley.com/doi...
ncbi.nlm.nih.gov/pmc/articl...
We plan to re-do the NGS panel a year after we get to a stable (hopefully we are there at 90mcg every 2-3 weeks) dose of Peg to see if Peg has been able to not only control my CBC numbers (hematological response - so far it has been effective) but also had an impact at the molecular level (to reduce the allele burden)....
Outcomes of JAK2 V617F-positive polycythemia vera and ET according to the JAK2 V617F allele burden
BMB Results Not Clear - Is this Common? 
Eye floaters
ET jak2 to PV
