20 year mystery possibly being solved

[Chaucer89]

Hello all,

A while back I wrote a long post and I thought I’d give an update. Basically the long story short, I was diagnosed with Polycythemia Vera when I was 14 (back around 2003/04) after testing positive for JAK2 and having high RBC. Then over the next year I tested twice positive and twice negative. After a major unrelated operation my bloods were in normal range and I was kept severely anaemic by my oncologist to keep them down (I eventually decided to take iron against his choices as I was suffering extreme leg cramps) and after my 4th JAK2 test came back negative I was told I didn’t have a MPD and was discharged. This was 20 years ago, the JAK2 test was new and I’ve seen that things have changed a lot in diagnosing an MPD. My bloods have always stayed in the high end of the range over the years but never enough to feel I could ask for investigations again.

Anyway in the last few years my RBC and Haemocrit have been slowly rising and now are right on the cusp of normal. I’ve always been curious about finding answers regarding why I had 2 JAK2 positive tests if I didn’t supposedly have a MPD. Was it because we were looking for something wrong that I just caught the MPD sign very early and it’s still dormant?

I happened to see a fantastic doctor recently for something unrelated and as we talked about my long and complex medical history he knew how much this had affected me and my life and on my behalf wrote to the haematology department to see if they could give me an answer. I really thought they would tell me just to go away and stop wasting their time but amazingly I have an appointment to see them next week.

I’m extremely anxious about it, I don’t know after all this time whether I want them to say I did have an MPD in the end after all this time and I was right or to say I dont and can move on somehow. Does that make sense? I obviously don’t want to be ill but it would everything make sense if I was? I can’t overstate how much the way that was all dealt with (badly I feel?) when I was so young has affected my life, being discharged so suddenly after finally getting an answer after 10 years of tests etc starting from age 9, not knowing for 20 years if it was going to come back or understanding the JAK2 results and no one to ask. I know a few of you were interested if I ever found the answer so I’ll update here when I see them if people are still interested. I just wanted to write this somewhere I think people will most understand.

[EPguy]

The Jak2 mutation for PV was discovered in 2005, see below, so your Jak2 tests would have been among the earliest in normal use. You're right a lot has changed. Likely the tests are more accurate these days. Also, there are several other mutations they look for now that were not known then. In PV they should check for Jak2 Exon 12 if your regular one (Exon 14) is negative. If ET is a possibility they also should check for CALR and MPL. You also could have none at all and still have ET for example. There is also deep gene sequencing that is suggested these days if MPN is suspected where they look for many other possibly relevant mutations.

Another new development since your last encounter is they now call our disease a cancer. This is good because it has brought lots more funding and attention to treatments. With that change, our condition is now commonly called MPN (Myeloproliferative neoplasms) rather than MPD to fit better to the new (~2008) cancer definition.

If you do have PV, our "normal" HCT is well below what they list on the charts, in the US for women it's usually 43 max, 45 male. Hope to hear your results from the experts you're seeing.

mpnresearchfoundation.org/n...

<<The first news came out on March 17, 2005: A team of researchers at the Cambridge Institute for Medical Research, UK, led by Dr. Tony Green, announced that they had discovered a single point mutation in the JAK2 gene that appeared in 97% of polycythemia vera patients they studied>>

[Chaucer89 in reply to EPguy]

That sounds about right, I was sure my first test was 2004 but my memory on that time is hazy at best so could of been early 2005 as I had my operation late 2005 and was discharged soon after that. If I remember rightly I was told as a kid that I was quite famous in the haematology departments of the various hospitals I was under as I was one of 2 children in the world to be JAK2 positive so yes must of been very early days! Funnily Dr Green from that study was my oncologist at the time.

[EPguy in reply to Chaucer89]

That is quite a history, to be part of history. I think you may have been part of Dr Green's pioneering studies before most Drs had access, that could explain the dates. I'm like you, keep good track of dates.

Do you have access to Dr Green's clinic or its successors now? In any case if MPN is suspected and your Dr does not suggest some sort MPN gene study that will be a good sign to go get a 2nd opinion.

[Chaucer89 in reply to EPguy]

I’ve never thought of it like that..I knew it was a new test but didn’t realise it was that early! Would be curious what Dr Green thought if I end up doing having a MPN after all these years. I’m not near his clinic anymore, I’ve moved to the other side of the country. I think where I live in the U.K. currently means I’m going to have to travel to find a mpn clinic if the need ever arises which will be tricky.. but that’s far off, if at all, yet. Thank you, very enlightening!

[hunter5582]

I think it is always better to know than not. Fear of the unknown is almost always worse than reality. Knowing the reality allows for better decision making.

The good news is that understanding of MPNs has progressed quite a bit since you were first diagnosed. Note the change from MPD to MPN as one step towards a different understanding of PV.

Genetic testing has also progressed. One of the things to look at now goes beyond the qualitative JAK2 test (Yes/No) looking instead at the quantitative test (mutant allele burden). I wonder a bit is back when you were first diagnosed if you were on the edge of the sensitivity of the current genetic testing due to your allele burden. That could account for the variable findings.

Hopefully the hematology office you have been referred to is a MPN Clinic. Most hematologists do not have the KSAs to provide optimal MPN care due to how rare they are. Note that pediatric MPNs are exceedingly rare. There are very few providers who have the requisite expertise.

Do please let us know what you learn.

[Chaucer89]

Interesting, thank you. I’m 32 now but I’m hoping the weird childhood history will get someone’s curiosity going if nothing else! I’ll certainly ask about genetic testing if they don’t go there. I’m hopeful they’ll actually do testing, rather than do what I fear which is just assuming by my current blood levels and old results and then tell me to just continue monitoring. I’ve been told to go to the haematology oncology department but I’m not sure if it has an actual MPN Clinic (I don’t think so). I suppose that’s something to consider if it comes about,

[Wyebird]

So glad you’ve posted. It helps mentally.I do hope you get answers soon. I think you will feel more at ease when you do.

I’d like to point out that you can have ET without having the high platelets. I was told this by my heamo.

Take a deep breath before your appointment. Relax best you can good luck

[Chaucer89 in reply to Wyebird]

Thank you very much, deep breaths definitely going to be needed I think!

[Hopetohelp]

That is a fascinating post. Yes please let us know your results. I would love to hear and hope it goes well

[Chaucer89 in reply to Hopetohelp]

Thank you, I will certainly write an update when I find out!

[SolasChoir]

My husband was also diagnosed with PVR in 2005 and has the JAK2 mutation. Well controlled now but for one thing: he was diagnosed with Multiple Myeloma in 2019 - which presented as a large plasmacytoma on an almost inaccessible part of his pelvis. A PET scan showed multiple plasmacytomas scattered throughout his body, resembling gunshot (i.e. particles from a cartridge, as fired from a hunting gun. Not rifle bullets!) We didn't get to ask too many questions - like - how come it was "missed" all those years, despite monthly blood tests? His positive attitude to life saw him through xx. His mm relapsed recently (now on steroids + revlimid and injects himself with... i think itsa type of heparin..?) Positive attitude continues (i am the worry wart! Though i pray. A lot 🙏)

Re your case (of some positive/ some negative JAK2 tests): i wonder... Did they check whether you might be carrying 2 separate blood type? 🤔 It is called chimerism. A law case in Australia some years highlighted this remarkable condition. A family were sued for social welfare fraud because DNA tests showed the wife could not be the mother of the 3 children for whom they claimed welfare increases. The father was, most likely, the natural father- and the natural mother was closely related to the parenting mother.. What was going on?? More complex blood tests revealed: wife carrying 2 different DNAs. The cells in her ovaries and womb had a different DNA than that found in her peripheral blood. Conclusion - at that time ? She had a twin sister (fraternal ?) whom - somehow - she had absorbed while they were both still embryos. Thus she had given birth to her sister's children... (i will find the references/ citations, if anyone really interested) However i think there may now be other explanations for that type of chimera.

God bless with your blood tests. And if they tell you "you are unique!" Remind them - there is nothing unique about being unique 🙂 What amazing people there are on this website!!

[Chaucer89 in reply to SolasChoir]

Thank you very much. I have read over the years various things that could explain why I had positive and negative results, from the capability of each lab to test for the JAK2 mutation (especially in the early days) to I think something about the amount of cells which contain the mutation can be low at the early stages and a blood draw may pick up such a low sample that it produces a negative result and vice versa. So it could have simply been luck of the draw! (Pun intended).

I have never even considered the idea of chimera blood. What an interesting idea, I think as I’ve had pretty much constant hospital monitoring since I was a very young for multiple conditions it would have been found if it was so but you did make me ponder for a second as I have a habit of developing very rare medical issues! Amazing story about the woman too.

I’m glad your husband is doing well despite it all, as you say it can be baffling how things like that are missed but it’s so easily done aswell if no ones expecting it. It took me 10 years of constant investigations to reach the point the doctors started looking at MPNs. I’ve no idea if it was just a fluke idea one of them had. Think we went through every disease in the medical textbook first.