As someone was declaring with a bit of overconfidence that MPNs are not hereditary, it is good to debunk several myths related to hereditary MPNs.
1. There are hereditary MPNs. Not as many as familial MPNs, but there are hereditary MPNs. pmc.ncbi.nlm.nih.gov/articl...
The mutations causing hereditary MPNs are called germline. Unlike the somatic mutations that cause most of the MPNs, mutations that can be found only in the affected cells, i.e. in blood and bone marrow, pathogenic germline mutations that cause MPNs are transmitted from parents to children and can be found in the DNA of every cell in your body. In familial MPNs, one inherits the propensity to acquire a pathogenic mutation during their lifetime that could lead to MPNs. Said mutation is often the same as in sporadic MPNs, a somatic mutation (e.g, JAK2V617F or MPL W515K/L). In hereditary MPNs, one inherits the respective mutation from their parents like one inherits eye colour. Having a germline mutation does not mean one would necessarily manifest signs of MPNs, though. Some people will have the disease, other people will not, despite having the germline mutation.
There are different mutations that can cause hereditary thrombocytosis, some on JAK2 gene, but much more on MPL, and other genes. TPO is another gene on which pathogenic germline mutations can cause hereditary thrombocytosis.
If you want to learn more about hereditary MPNs, the studies below presents some of these germline mutations that can cause them:
There was a dogma in the past that MPNs are never hereditary, which contributed to hereditary MPNs being understudied. We should not reinforce said dogma. It has done enough harm. There are few studies on hereditary MPNs, and for hereditary thrombocytosis there is barely any guideline on diagnosis and treatment.
2. There was this other myth that hereditary thrombocytosis never transforms into myelofibrosis or AML, yet studies show that hereditary thrombocytosis can and does transform into myelofibrosis and AML. This is understudied, and the dogma that hereditary MPNs are somehow benign might have contributed to this. The studies that exist do show that hereditary thrombocytosis does transform into myelofibrosis and even AML. Given how many germline mutations there are that can cause hereditary MPNs, transformation might depend on the type of mutation, but also on other factors.
Thanks for posting the links. I just added some on the Familial MPN thread that you responded to.
I think that the evidence is clear that patterns of inheritance play a role in classic MPNs as well as Inherited Erythrocytosis and Thrombocytosis. This is not understood as well as it needs to be. The involved genetics are complex and need further investigation to better understand how the patterns of inheritance work.
There are some in the medical community that are not up to date on this emerging science. This is unfortunate as it leads to misinformation being relayed. I suspect that many cases of Familial MPNs and the other inherited variants have gone undetected for a long time due to this lack of awareness.
At the same time, we need to not panic that the myeloproliferative disorders will automatically be passed on. It is more complex than that. It also depends on what form the genetic variant takes. You correctly identify the difference between a germline and somatic mutation. In addition, germline mutations can be autosomal dominant , recessive, incomplete dominant or codominant. There is even more complexity to the genetics involved than this. There is plenty to learn to fully understand.
I agree that more awareness is needed regarding the genetics of Familial MPNs and the Inherited myeloproliferative disorders. It is also important to understand why there seem to be clusters attached of other blood cancers like lymphoma. One avenue worth investigating has to do with the role of inherited telomere abnormalities. pmc.ncbi.nlm.nih.gov/articl...
There is much to learn. We can support the research that is needed through our advocacy and willingness to participate in the research.
It's not before time that some serious research was done because I long suspected there are familial links. When I was diagnosed in 2006 I asked the question of my then consultant who had a very good reputation in Haematology but he categorically stated it was simply bad luck and that was why it was called Idiopathic. I pointed out my Grand-Mother had some type of Leukemia / blood cancer (died in 1950s before I was born) my Mother had died of Myeloma, a cousin who wasn't local to me and I didn't have contact with also had a type of blood cancer. But he simply dismissed it all with a smile and said he was sorry but I was just unlucky in life's lottery.
I know it's cropped up several times on the Forum over the years and there's a raft of anecdotal evidence so I'm pleased that finally it's on the agenda and some dedicated folk are hopefully delving deep into the subject which in the future might help identify those at risk and more if they utilise AI 😲 (you never know).
Yes, I asked about "inherited" bone marrow and blood diseases back when I was diagnosed with erythrocytosis as my maternal family line is littered with examples but was told there was no evidence.
Had I been taken more seriously or attended a more major hospital perhaps the investigation would have stated earlier.
I placed a post on this topic eight years ago. I had joined this forum the previous year and was taken aback by a fair amount of members who had more than one person in their family with an MPN.
I don’t know if there is any connection, but my first cousin had ‘Non Hodgkins Lymphoma’ successfully treated. However, why I placed the post was my Father died in his early forties of a heart attack (no family history) and it did make me wonder if there was a possibility he had an undiagnosed MPN.
I have ET and my brother has Non Hodgkins Lymphoma. I think there are quite a few of us MPN patients who have relatives with blood cancers. Interesting!
Thankyou for raising awareness for this! I pray that this subject gets more research for both of my daughters sakes who one is confirmed to have inherited germline Jak2 mutation from their dad, the other awaiting genetic testing results. It stems back to his mother, his mother's sister also has ET aswell. Why more research hasn't been done is beyond me when so many people have family links with blood issues.
Research on hereditary thrombocytosis has not been done in the past for various reasons, all of them reflecting bad on both medical practice and medical research.
One of those reasons is that the initial hypothesis was that this illness is not inherited, but acquired, that it happens due to age, and it is mostly found in people above age 60. This means that people who did not fit these criteria fell through the chairs and were not diagnosed. Initial bias fuelled future bias. Now we know that a good part of the people diagnosed are not only younger than 60, but they are 40 and under. Many of the people with HT were most likely misdiagnosed with reactive thrombocytosis for a while, as they showed elevated levels of platelets at a young age, when it was considered unlikely for them to have ET. Plus, there is no guideline on how to diagnose pediatric ET/HT. At least, there wasn't one when I looked for it last year.
Another issue that kept hereditary thrombocytosis undiagnosed and ignored by research is the belief that HT is, somehow, "benign." As one is born with it, it was thought that, since it does not enter the traditional clonal disease definition, it also does not transform into myelofibrosis and AML. This aspect was severely ignored. It was only in the late 2000s when a couple of studies on some families showed not only that HT can transform into myelofibrosis and AML, but that depending on the type of mutation, transformation can happen at a higher rate than in ET and happen earlier in life in some families. Despite this information, you can hear hematologists in 2024 swear that HT is "benign" and insisting one should not follow HT patients as closely as they follow regular ET patients. Which means HT patients are left a bit on the side.
Another factor that had contributed to the lack of research on hereditary thrombocytosis comes from a blend of convenience and what I call arrogance. MPNs are considered rare illnesses, and for a long while the focus of research has been on the JAK2V617F mutation which is involved in most PV cases and about half of ET cases. There was a big name in MPN research that went so far to say 10 years ago that one should not look or care for other mutations than JAK2V617F and CALR when diagnosing ET. This means that anyone with a different mutation, if this advice was followed, was put into the "triple negative ET" basket. These days we are learning that germline mutations seem to be behind a good part of these "triple negative ET" cases, including mutations that cause hereditary thrombocytosis. Research on hereditary thrombocytosis is a couple of decades behind more rigorous research on ET itself. Studies are few and treatment recommendations sound pretty bleak: "there is no evidence of efficacy" for a treatment or another (meaning there are no studies on treatment efficacy in HT patients, these patients have not been studied).
Given the biases and preconceptions of the past, we are where we are. Some efforts are starting to happen, but research on hereditary thrombocytosis is a couple of decades behind research on ET. And while decades of ignoring HT makes it look like it is extremely rare, once proper efforts are put into diagnosis and research, we might learn that it is not so rare after all.
So very true, I really hope something new comes to light for everyone, I also believe alot more people have it just not diagnosed. It's almost like some people don't believe me when I say about my daughters
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triple negative pre-fibrotic primary Myelofibrosis with SH2B3 mutation 
Recently diagnosed with ET
INF, allele and more
Is ET a blood cancer?
