Homozygous JAK2 / PV. Started Besremi January 29th. Previously on Pegasys at 135mcg effective dose. The attached image spells everything out for the most part with the counts and corresponding dosage previous to labs.
One variable I'm unsure of is my latest lab was taken only 4 days after my last dose at 375. My other labs were all done a day or two before I was due for my next dose, and I don't know how much our counts fluctuate in the duration of the 2 weeks injection schedule. So this may skew things a little, but I'm still optimistic. I'm going to hold steady at 375mcg and let things settle out. It's possible I've become slightly iron deficient and my counts may drift up a bit more, but I think I'm close to an effective dosage. Fingers crossed.
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jon1972
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it looks like you are on a good path with the Besremi. Holding steady makes sense. Given the schedule of phlebotomy you have had, it is certain that you are at least somewhat iron-deficient. That after all is the purpose of the phlebotomies. Hopefully as the Beremi fully kicks in you will no longer need phlebotomies at all and can let your iron levels come up without erythrocytosis evident.
Please do keep posting how things are going. It is really nice for us to be able to compare notes.
Thanks Hunter and will do. I have gotten a lot out of this forum and try contribute as much as possible. I've only had those 4 phlebotomies this year and had not needed one for over a year before that while on Pegasys, but they were all 500cc's. I don't know how many it takes to become deficient, but yeah I figure it's at least going to be a little. I'm not sure if any of my CBC or CMP numbers can reveal any clues about my iron level. If anyone has any info on that it would be appreciated.
The erythrocyte numbers on your CBC can give a clue as to your iron status. You can also simply have an iron panel done. Note that there is more to iron status than ferritin. Not sure how much that matters at this point. While I check iron levels periodically, I am more focused on how I feel. Feeling good = doing good. Reducing risk of thrombosis (HCT<45%) without unacceptable adverse effects remains my goal.
For your homozy status, was that a specific test your Dr ordered, or can
it be figured from typical BMB or other data? As in recent reports,
this seems important for INF response.
Your point on the timing dose vs CBC is interesting. Do you know what timing you will have on the next CBC? But your WBC is trending up with this post dose CBC so at least there the effect was the other way.
Yes they are great numbers. I was a little surprised to not have any flags this month. It was much harder to balance the counts with Peg, where I was frequently too low on whites while high on the reds. As for the homozy part, I just went back and looked at the paperwork and that was originally from a genetic blood test. I'll post a couple additional images of that. Now that I look again I don't know if I'm misreading that it's homozy, but that was my interpretation as I understand it to be the more aggressive form of JAK2.
I must say the indication of primary MF is a little troubling. I don't remember seeing that before and nobody has actually mentioned that to me before.
They have a generic statement that higher AB (>60% here) correlates to homozy. True but not specific. I've also seen the idea of more aggressive for homozy, while also generally better response to INF as my recent posts (avgs don't predict indiv response of course).
But more important, some confusing info here. They show jak2v617phe, and also jak2v617F. "F" is what we usually see, and what I have. Your "F" has the unspecific >60%. The other one, "phe" has AB of only 18%. This lower value would tend to be heterozy, but that's a side issue at the moment. Are there two different mutations in your sample with different ABs? (Phe and F) Is "phe" associated with MF? That is their implication. Or are they giving incomplete/wrong info?
You have good reason to ask a lot of questions next visit, and entitled to be displeased with this vague unexplained result..
I think we may not have a clear understanding of these abbreviations mean, at least I don't. I will have to do some reading. Maybe they're just providing more details about the location or something? I see they're listed the p.val617phe under the column "alteration". These are all the tests I've had done:
- Initial dx: 1/4/2018 v617f detected (the one that says >60%)
- Initial dx: BMB 2/12/2018 V617F detected
- 1 year later: 2/28/2019 Vanderbilt v617 (phe) = 18%
- 2+ years later: 9/8/2020 tested by mayo clinic V617F detected at 4% (note the effect of Peg on allele).
That's a really good AB reduction. Consistent with the homozy being responsive. Was the >60% reading also from Mayo?
The AB at Vanderbilt actually is plausible being on the path to 4%. It is typical to see a steeper decline at the start on INF, if there is one, so the AB timeline (>60-18-4) is consistent with that idea.
Reading the 2nd sheet just below Interpretation Summary, , I think phe means phenotype, with "F" being the specific subset of the phenotype- A wording style at Vanderbilt. All makes sense then and no new mutations to understand. But the comment re MF is unusual. I think they compare Jak2 broadly to CALR and at least for certain CALR types, there are progression diffs vs Jak2 from what I've seen, but that applies to ET in general.
But why is CALR relevant? You have PV and CALR associates with ET, so they are comparing ET to PV, not too insightful here. It's an arbitrary comparison I think. Why not also compare triple neg or ET's MPL while they are at it? I'd ask Dr why that part is in there.
The 60% reading was sent out to a place called NeoGenomics. I forgot that I had another reading this past year too as they try and check my AB yearly. There's that "phe" mentioned again. My guess is it has something to do with the location on the dna strand where the mutation occurs, but nothing out of the ordinary. My specialist at Cleveland Clinic who ordered this said the 6% vs 4% AB is clinically insignificant and there could be that much difference in simply testing the same sample twice.
Result:
CALR - No variant detected (Reference sequence: NM_004343.3).
JAK2 - A sequence change, c.1849G>T (p.Val617Phe) in exon 14, was
detected at approximately 6% allelic proportion (depth of coverage at
change 1530) (Reference sequence: NM_004972.3).
MPL - No variant detected (Reference sequence: NM_005373.2).
I may have found some info. I believe Phe stands for "Phenylalanine" where "Phe" replaces "Valine" in our mutation. Hence V=>F(Phe) See reference.
This is how our Jak2 gets broken. My guess is they got tired of writing Phe and so F is a short hand description for Phe.
Interesting that, other than this UK reference, the use of Phe is mostly in early reports (near 2005) when the whole subject was new. Later ones tend to the shorter "F".
<<JAK2 p.Val617Phe (V617F) Mutation Status>>
<<The substitution of Valine to Phenylalanine...>>
Homozygous means both alleles carry the mutation rather than just one. I'm not exactly sure how they determine it, but EPguy pointed out above that there was a generic statement with regard to my allele burden being over 60% is consistent with homozygous and more aggressive disease. I don't have a better answer unfortunately. I might pick my specialist's brain about it next time I see him.
You bring up a good question. I think the lab needs to specifically look for this feature. But likely few or none in this forum has this data, only in certain clinical trials would they look for it. Its significance is not recognized in our treatments to my knowledge. I would like to get it if Dr would agree, but at <20% AB likely I have heterozy.
As discussed here, if your AB is well over 50% odds are higher you have homozy, but that's not definite.
--
It gets complicated, if you like more details:
I think Homozygous is related to Uniparental disomy (UPD). <<UPD occurs when both chromosomes of a pair or areas from one chromosome in any individual have been inherited from a single parent.>>
This means it happened before birth. But our mutations usually occur after that. So there is "Aquired UPD"
<<Acquired uniparental disomy (aUPD) is a common and recurrent molecular event in human cancers, which leads to homozygosity for tumor suppressor genes>>
Thrilled for you. I’ve ET and my iron has gone as low as 93 ( female). I think I’d rather be a little iron deficient that have to go through vivisections. My haemoglobin actually went up a little when I started Peg. Let’s hope all settles down nicely for you.
Hi, The mutation that is called V617F actually stands for the substitution of a Phenylalanine for a Valine (which is the normal amino acid in that spot). For some reason the labs always makes F short for phenylalanine (I guess based on how it sounds). It really should be called V617Phe and they have actually put that in one of those results ie. "V617Phe (V617F)".So no mystery, it is only different nomenclature at different testing sites.
Going from over 60% to 4% is a very nice result for your allele burden though so you are definitely responding and that makes all the 'possible' progressions less likely as far as I have understood the research. Lauren
Thank you so much for that explanation Lauren. As for the AB, as great as that drop sounds it was shocking how quickly my blood counts got thrown off and my disease symptoms came back with a vengeance from missing just one week on Pegasys after being completely controlled for 1 year w/out phlebotomy.
I understand a very small number of people (~5%) go into clinical remission while using IFN with their AB going to an immeasurable amount and allowing them to discontinue injections altogether. I read about that the fist time back in 2018 when I was first diagnosed. It was one of the big reasons I pursued being put on it. Anyway, I'm pretty sure the data was based on Pegasys and not other IFN's. I don't think Besremi was even out at the time. Hopefully Bes will prove to be even more effective in the long run.
I pressed for INF right after diagnosis, had to take hydroxyurea first but it did not agree with me (I didn't agree with it either). Lots of research going forward now so it is a much better time to have this disease than when my father (ET) and uncle (PV) had it. All the best to you and keep us all posted.
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Started Besremi
Besremi working well- 150 mcg every month instead of bi-weekly 
