A more general question: What is the source of ET/PV? Does people with PV/ET had it before birth, from childhood, or it appeared later? How?

[samiris]

For instance, when a person is diagnosed with PV or ET at 60 or 50, was it hidden in their body asymptomatically, carrying disease for a long time with no symptom?

[ladyanello]

PV generally is thought to be an acquired mutation, not genetic, although there is a form that is familial which is now thought of separately from classic PV, I think. Onset is a bit of a question now too - used to be an older person's disease, being diagnosed younger now and there is a suspicion adults can have it almost asymptomatically for years before diagnosis. Don't know that it's seen in children. Just from my reading about PV, not a doctor and things are changing quickly.

[Manouche in reply to ladyanello]

All mutations are genetic. I suppose you got confused with the terms « genetic » and « congenital ».

[ladyanello in reply to Manouche]

Sounds right, Manouche.

[samiris in reply to ladyanello]

Thanks Ladyanello for clear explanation.

This issue about PV is sometimes confusing in families, even with educated members, that had never heard about it when one is diagnosed with JK2+ and PV or ET in that family. They reasonably assume it as acquired than genetic, but still remain puzzled. Yes, it's too complicated, life science needs many years study till can give a clear explanation.

[Mpncoda in reply to samiris]

Yes, my hematologist said PV and ET is generally not inherited. Seems there’s not a clear answer here.

[Manouche in reply to Mpncoda]

To sum up: A disease can be inherited, congenital, or acquired.

[MPNBlog]

Hi samiris. Both my brother and I have PV. I was diagnosed at 68 and he at about 65. The symptoms and characteristics we have experienced so far are quite different for each of us. MPNs are caused by a mutation in the gene/s which is acquired after you are born. We were told that PV isn't inherited, but that we must have inherited a pre-disposition to the mutation.

Here's a link to a 2013 article titled "Inherited predisposition to myeloproliferative neoplasms": ncbi.nlm.nih.gov/pmc/articl...

It says "...familial predisposition has been recognized for many years in a subset of cases and epidemiological studies have indicated the presence of common susceptibility alleles."

I think that I had PV for at least 2 years prior to diagnosis due to symptoms that I had sought medical advice on. While MPNs are mostly diagnosed in older people (mutations in genes mostly take a while to appear), I know of a case of an 18 month old girl with ET. I've been told there is no point having my children tested as even if they are susceptible, nothing will probably show up until they are much older. There is currently a study underway in US to try to get some more explanations for the familial occurrence of MPNs, and to try to help understand the disease generally. I tried to enrole, but you had to be in the US for the required blood tests. I hope that helps.

Best wishes.

[spolak in reply to MPNBlog]

Do you recall where you saw info about this familial US study?

[MPNBlog in reply to spolak]

The MPN Familial study is being done by Dr Angela Flieschmann in her labs at UC Irvine, USA. The research is part funded by MPN research Foundation: mpnresearchfoundation.org/T...

Also see: wearempn.org/why-does-mpn-r...

which says: "MYELOPROLIFERATIVE NEOPLASMS (MPNS) CAN MANY TIMES RUN IN FAMILIES BUT RESEARCHERS DON'T YET KNOW WHY. THE CENTRAL GOAL OF OUR MPN FAMILY STUDY IS TO IDENTIFY RISK FACTORS THAT MAY PREDISPOSE SOME PEOPLE TO DEVELOP AN MPN. THIS STUDY WILL ALLOW US TO UNDERSTAND THE GENETIC FACTORS UNDERLYING FAMILIAL MPNS AND PROVIDE A POTENTIAL SOLUTION TO REDUCE THE RISK OF MPN IN FAMILY MEMBERS."

I applied in March 2019 when the study opened. It looks like you can still apply (if you are in US). There's a link in the second url above. Hope that helps.

[Wyebird]

In my, case breast cancer uk had a sample of my blood in august 2005 for research only. My heamo managed to get the blood analysed in dec 2015 2 months after my diagnosis. My genes had not mutated in 2005.

[RobPV in reply to Wyebird]

Wow! That is amazing. I truly find it unbelievable that the NHS keep blood samples for so long even after testing. Obviously they do for research purposes. Unfortunately I cannot remember having a blood test before 2015,when I was diagnosed. I would like to know when this happened to me. I've often wondered if the mutation was caused by some sort of injury or event. Was it a bad decision or purely fate.

[Wyebird in reply to RobPV]

Yes I was surprised. I took part and am still part of clinical research. I had a huge questionnaire to fill out and they are still sending me questionnaires. They are following my life. It’s all research into breast cancer.

My heamo did say that the sample might not be good enough as it was in storage but the results indicate it was. NO MUTATION august 2005!!

[MPNBlog in reply to RobPV]

Hi RobPV.

The only other environmental factor that I am aware of with some evidence that it predisposes people to PV is exposure to benzene. There are several clusters documented in the US in rural Eastern Pennsylvania near toxic waste sites: pubmed.ncbi.nlm.nih.gov/191... From memory, in one cluster, 4 people in the same street were diagnosed with PV which led to an investigation.

Potentially obesity and excessive smoking could be risk factors according to this study: pure.qub.ac.uk/en/publicati...

[samiris in reply to Wyebird]

Hi, Wyebird: This is great observation, no mutation in 2005 but mutation in 2015!

Sometimes when people diagnosed with PV ask doctor about the onset of PV appearing in their body, doctor just says "We don't know because we don't have blood-test/BMB results of all times since birth". But in your case, observations indicate that the goddamn mutation appeared in between 2005 and 2015. Now next-step question can be: Why? Could lifestyle (diet, physical activities/exercise, stressful life, trauma, etc.) prepared conditions for that mutation happening? (I don't expect you to answer these fundamental question, just came to head).

Take care!

[Wyebird in reply to samiris]

Had a stroke October 2005 . This is what brought about the recovery of my sample. DID I MUTATE BETWEEN AUGUST AND OCTOBER? Thus causing my stroke.

The general view is that is not he case.

I was having annual blood test as a result of the stroke. tHat is what led to my eventually et diagnosis.

[JabON]

I was diagnosed with JAK2 mutation in 2019 after a routine blood test at my local hospital . They also had the results of a full blood test from 2012 and there was no sign of the mutation then.

[Wyebird in reply to JabON]

They will only find a mutation if they look for one x

[Hydrox]

Hi, I was diagnosed with ET Jak2+ in 2012 after a blood test. My platelets were in the 900s and my gp checked my records and found a blood test taken 13 years previously had also been in the 800s, but not picked up by anyone. After being diagnosed I realised that I had symptoms for a long time but did not realise. I used to bruise very easily and had balance problems, I also bled a lot if I cut myself, but did not suspect anything untoward. Being one of 14 children, I am the only one with an mpn.

[samiris in reply to Hydrox]

Hi, Hyrox: Thanks for your explanation.

It's not patient's job to realise what is right and what is wrong, it is GP's duty. When GP neglect to check the issues and record carefully and is careless about our health, what patient can do? Early diagnosis is a big deal for treat the disease at much less costs, lower risks and pain. It's not good the GP did not see any alarming signal for your ET. These diseases advance to higher and more complicated levels when diagnosed late.

Hope you are doing well now!

[Hydrox in reply to samiris]

Doing great, no major problems, walk 5 miles every day as I live in the countryside. I get tired more but it could be my age,72 now, keep on being well.

[JaK2ET]

From what I have read so far, both CHANCE and FATE may be involved in the origins of MPNs.

Chance - that you acquire one or more of the relevant genetic mutations (risk increases with age, as you have been exposed to the world for longer and the ageing process has had longer to make things go wrong, and risk may also be increased by life stresses and choices)

Fate - that you are born with genes which cause the mutation(s) to have a worse outcome and/or make you more likely to get mutation(s) in the first place

A striking feature that I have observed during my short period of membership of MPN Voice is how often MPNers mention having a close blood relative with an MPN and/or a close blood relative with another inflammation-related illness. To me this suggests that inherited genes must be playing a part and the scientific research seems to support that idea to some extent.

[MarybellM]

Re when and how PV begins... My husband was a regular blood donor and his PV was picked up when he got his thumb prick test. He was told to go to his GP as his iron was high (I think...) Anyway, my point is that he didn’t have this issue for the previous blood donation, so it had actually developed in the space of a few months. There just doesn’t seem to be a straightforward answer to what causes people to develop MPNs but I just hope there’s loads of research going on.

[samiris in reply to MarybellM]

Thanks for this! Any exposure to high-energy radiations (power plant, etc.), chemical hazards (benzene, etc.), severe trauma, or ...?

We really don't know the environmental & social hazards around us, they may play key roles in development of such mysterious diseases!

[MarybellM in reply to samiris]

Hi Samiris. We live on a small remote island in the Outer Hebrides. We are close to the sea. My husband works from home doing accounts. So, nothing really obvious as far as I can think. Interestingly, my cousin (ie no relation to my husband) recently got diagnosed with PV and ET (plus prostrate cancer) He’s about the same age and lives about 5 miles away.

[JaK2ET in reply to MarybellM]

I was interested to read that your husband's PV was picked up following a blood donor session. I last gave blood in 2014 and 2015 and wanted to continue but didn't feel quite well enough in the subsequent years. It is my suspicion that my ET might have started around 2016 or 2017 (one stressful event was my mother's final decline and death in late 2016 to early 2017). Following my actual diagnosis in Feb 2019 I contacted the Blood Transfusion Service and was told that whole blood donations are not regularly tested for platelet count, so ET would not be picked up that way. PV is a different matter of course, because a potential donor's blood is checked for iron/haemoglobin every time ...

(Sad to note, the BTS also confirmed that because of the ET diagnosis I would not, under present guidelines, ever be able to give blood again. I had seen my mother in hospital being given blood from packs in her final days and wanted at least to help make up for what she had received ... )

[MarybellM in reply to JaK2ET]

I’m sad to hear about your mother. Now that you’re talking about stressful events, there was a major one in our lives in 2005, but my husband’s PV didn’t develop till approx 10 years later.

[Dovme]

My ET was picked up during change of GP who checked through past blood counts. They do them here regularly. No history in my family that l am aware of.

[samiris in reply to Dovme]

It needs a comprehensive research work to figure out about the cause(s) of disease. GPs don't have time and competency to do that job, they are practitioners, not scientists. Some GPs are ignorant about out-of-range counts in blood test results, but some are more careful, refer to specialist to look at issues.

[Dovme in reply to samiris]

I agree Samiris am happy with my new GP he is great very thorough.

At the time l was referred to a haematologist my platelets were only around 350. So my GP was good to spot it.

I have not been exposed to any power plants etc. l lived in rural France for a while near farms possibly fertilizers? Doubtful! Other then that l have always lived in big cities

[Cat1001954]

I was told blood in urine and pain was constant uti s. I had blood test every month and they kept telling me do another test in a months time. Eventually they sent me to see heamatologist and had Ben and I have triple negative ET. Not sure what it means the first bit was diagnosed in august now on hydroxycarbamide 500mg day