Tet2 allele frequency

[Janis12]

Hi Folks, after requesting my Tet2 VAF recently (diagnosed with ET 2020) my BMB was re analysed from 2020 and came out at 32%....when reading the letter I nearly chocked on my 'Graze marmite crunch' (very addictive). I have been on hydroxy since diagnosis and five months ago started the transition to Pegasys, 45mcg every two weeks. When I asked in clinic for my VAF which was also requested by Claire Harrison (a shared care arrangement) I was told that whatever it turned out to be the treatment would be the same. To me that's a mighty high figure and now I am beginning to wish I had not requested it, ignorance is bliss etc etc. I believe that Peg is not as effective at reducing the VAF in Tet2 mutations. Could I just ask you all, do we need to have a BMB to check the VAF or can it be carried out with a blood test, I really do not fancy having another one of those bad boys. |Any words of support or opinions would be much appreciated, meanwhile I think I must eat the whole bag of Graze marmite crunch instead of half...it may just cheer me up. Thanks to you all.

[EPguy]

I've had VAF both ways at Dx and my Jak2 result was different for each. (19% BMB, 14% blood) My Dr says it's fine to use the blood value, but only that the same type should be used to look for changes over time. So you should get a blood reading early as possible in the PEG course to look for comparable changes.

There are reports in prior posts that Jak2 results are very close with either method, but my experience at least shows how it can differ. Likely there are fewer reports comparing TET2 by source making same-source esp desirable. Other members should have further experience.

In this reference it shows TET2 can also be tested either way:

dovemed.com/common-procedur...

[Janis12 in reply to EPguy]

It makes sense to see where I stand now after 5 months on a very low dose of Peg and use this as my base line. I know the treatment will be the same regardless but I feel if the Peg is having an effect on my allele burden then it is an incentive to put up with the side effects (increased muscle and bone pain). I know the TET2 mutation is a driver of inflammation so that in itself may be causing much of the 'aches and pains' and I wonder if a reduction in the burden would help with this particular problem. Many thanks for your response, the reference to TET2 made an interesting read.

[ainslie]

allegedly doing VAF tests are more accurate from BMB than with blood but most experts are fine with blood, as EP Guy suggested it might be a good idea to do a blood one now to compare and as a baseline and then just do blood ones to monitor

[Janis12 in reply to ainslie]

There is some interesting reading around this subject but I definitely feel I would rather have a JAK2 mutation than a TET2, the knowledge around JAK2 seems greater and more predictable but sadly we do not have the choice. Best wishes.

[EPguy]

I noticed in your prior post that TET2 is your Driver mutation. Are you Jak2 negative? In the past this term has been reserved for Jak2, CALR or MPL in MPN disease. So Dr Harrison is calling TET2 a driver mutation? It would point to improved understanding of this mutation, and having its value at least once in both BMB and blood should be useful info considering its less deep knowledge base.

[Janis12 in reply to EPguy]

Yes I am Jak2 negative and Dr Harrison has said the TET2 is my driver although I did read somewhere that 10% of the elderly population has the TET2 mutation (without a blood cancer). The deeper you dig the more interesting it becomes.

[EPguy in reply to Janis12]

A good sized set of elderly also have benign Jak2 allele, but at low levels. Agree on the interesting, Dr Harrison must be quite interested in your case, I think it's unique at least in this forum.

If TET2 is more specific to inflammation, something like NAC or other anti-inflammatories might be of interest. This is a specialty of Dr. Angela Fleischman. Has Dr. Harrison discussed inflammation in particular? IFN has a complex action in this area.

[Janis12 in reply to EPguy]

She has mentioned it only from the point of view that TET2 is a driver of inflammation and most likely the cause of my long standing muscle and joint pain. I have seen a number of specialists over the years relating to these symptoms (Neurologists, rheumatologists, orthopaedics and pain clinic specialists) and all they have come up with is mild osteoarthritis and a desiccated disc between L5 and S1 and I also have muscle fasciculations which started after a very long period of stress (18 years) came to an end. Apparently my body was so accustomed to continual levels of stress chemicals that when they all switched off the muscles reacted in this way, I was told by the neurologist that I would probably never be free of it......more interesting stuff!! I will have a look at Dr Fleischmans views on inflammation and also discuss this again with Claire Harrison. Thanks a lot for this information.