Hi, just wondering if anyone is aware if ET is hereditary ?
I was diagnosed five years ago, I'm JAK 2 positive ( although to tell you the truth, I'm honestly not sure what that means !)
i have literally just found out, through a family member, that my cousin, also has ET. Unfortunately he lives in a residential care home quite a distance from me, and I'm unable to ask him about it.
I currently take hydroxycarbamide , but it seems that he isn't on any medication for it.
I understand this is a very rare condition, so alarm bells are ringing as to whether it is hereditary.
Thank you .
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Catbells66
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I have PV, and while they're a lot alike, they're also somewhat different, and there has been some reporting here on MPN-V that ET may also progress to PV, so I didn't want to just give you an off-the-cuff answer.
When I looked, I found this:
"Inheritance
Most cases of essential thrombocythemia are not inherited. Instead, the condition arises from gene mutations that occur in early blood-forming cells after conception. These alterations are called somatic mutations.
Less commonly, essential thrombocythemia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When it is inherited, the condition is called familial essential thrombocythemia.
So the clearest answer is No, and yet, yes- sometimes...
To help you understand what Jak2 means and why it's important:
What is a Jak2 mutation:
The Janus Kinase 2 gene, called JAK2 for short, provides instructions to cells for making the JAK2 protein. This protein promotes cell growth and division and is especially important for controlling blood cell production within the bone marrow. This test looks for mutations in JAK2 that are associated with bone marrow disorders that cause the production of too many blood cells.
The bone marrow disorders caused by JAK2 mutations are known as myeloproliferative neoplasms (MPNs) in which the bone marrow produces too many white blood cells, red blood cells, and/or platelets. Some of the MPNs most commonly associated with JAK2 mutations are:
Polycythemia vera (PV)—the bone marrow makes too many red blood cells
Essential thrombocythemia (ET)—there are too many platelet-producing cells (megakaryocytes) in the bone marrow
Primary myelofibrosis (PMF),Primary myelofibrosis (also called chronic idiopathic myelofibrosis, agnogenic myeloid metaplasia) is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar-like material. Over time, this leads to progressive bone marrow failure
The primary JAK2 test is JAK2 V617F, named for a mutation at a specific location in the JAK2 gene. JAK2 V617F mutations are usually acquired as opposed to being inherited and results from a change of a single DNA nucleotide base pair. In JAK2, this kind of mutation, called a point mutation, replaces the normal amino acid valine (abbreviated V) with phenylalanine (abbreviated F). This amino acid change results in a JAK2 protein that is constantly "turned on", which leads to uncontrolled blood cell production.
Other mutations in the JAK2 gene are also associated with MPNs. Over 50 different mutations have been identified. There are tests available to detect mutations in JAK2 exon 12 and to identify other non-V617F mutations."
I hope that you find these helpful.
May I suggest that you consider speaking to your hematologist/oncologist about possibly changing over to an IFN- because while hydroxyurea [the US term for hydroxycarbamide] may be effective at reducing cell counts and thereby risk of clots, it has not been shown to be effective at preventing disease progression to myelofibrosis or leukemia.
Remember, the goal is to live well now, but also to avoid having our disease progress to the worst case scenarios of MF [myelofibrosis] or leukemia.
As a physician assistant, I tend to want to provide more rather than less information, which I understand can be a bit overwhelming at times.
If there is anything you'd like to correspond further about- questions, relevant studies, etc., please feel free to reach out any time- we're all in this together- [even though we have to decide what to do separately 😇].
On this forum there are a surprising number of familial MPN cases. Hunter is one. It's not a scientific sample but it seems more than coincidence. The official info usually says there is no such connection.
The answer to your question is rather complex as the answer from PhysAssist indicates. There are a couple of key things to understand, including the difference between an germline vs acquired mutation.
A germline mutation is an inherited mutation. It can be passed on to subsequent generations. An acquired mutation is not present in the germline. it is acquired at some point after the egg is fertilized. Even when this happens en utero, it is considered an acquired mutation. Note that this is relevant to MPNs.
The JAK2 mutation is an acquired mutation. It cannot be inherited. However, it is known that MPNs with the JAK2 mutation can cluster in families. This is referred to as Familial MPNs. A prevailing theory is that there is a genetic predisposition to acquiring the JAk2 mutation, the JAK2 46/1 (GGCC) Haplotype. This haplotype is something that can be inherited. Here is a bit of information about this issue.
I have a JAK2+ PV. My daughter has a JAK2+ ET that looks like it may be PV. My son is JAK2 negative but has idiopathic erythrocytosis. My daughter and I are both positive for the JAK2 haplotype as well. We are participating in one of the Familial MPN studies.
Technically family members can be tested for JAK2 or one of the other driver or non-driver mutations before they become symptomatic. The issue is that insurance will not pay for it without a reason. I think to cost is around $600.00 for the most basic qualitative test but you would have to check to be sure. labcorp.com/tests/489420/i-...
We also did the 23&Me genetic analysis which did also detect the JAk2 Haplotype. Do note that this is not considered a medical grade test. It is for more general interest and any result would need proper follow up. This can be done for under $200.00.
It is now known that the JAK2 mutation can be acquired in early childhood but take decades to manifest as a MPN. There is information available about this in the literature.
There is an additional issue that is relevant. Some people develop the JAK2 mutation but may never manifest as a MPN. This is referred to as Clonal Hematopoiesis of Indeterminate Potential (CHIP). en.wikipedia.org/wiki/Clona...
So that was a bit of a long answer to your question. The issues are complex and the underlying issues are not completely understood. My thought on this is that the predisposition for MPNs likely can be inherited. Whether any individual manifests a MPN is dependant on a combination of genetics, environmental exposures, random chance, and likely other factors we do not know yet. At this point, I do not see any value in paying for expensive genetic tests in the absence of any symptoms. Even if someone tests positive, there is nothing different to be done. We all need to reduce our exposure to carcinogens. toxins, mutagens and other environmental hazards that might be a trigger for MPNs. These things are triggers for other cancers too. I think the best thing to do is to assume that if a family member has a MPN there is likely an increased risk of someone else developing a MPN but not a huge risk. Just use a bit of common sense reduce exposures to anything that could cause a problem. Pay attention to CBCs and other routine labs and respond promptly is something does show up.
This was perhaps the most important section for this discussion:
"There are 2 basic types of genetic mutations:
Acquired mutations. These are the most common cause of cancer. They occur from damage to genes in a particular cell during a person’s life. For example, this could be a breast cell or a colon cell, which then goes on to divide many times and form a tumor. A tumor is an abnormal mass. Cancer that occurs because of acquired mutations is called sporadic cancer. Acquired mutations are not found in every cell in the body and they are not passed from parent to child.
Factors that cause these mutations include:
Carcinogenic chemical exposures. [including tobacco and other mutagenic substances toxins]
Electromagnetic radiation. [ including X-rays and all types of UV, of which UVC is most damaging]
Age [Biphasic: Childhood- related to rapid cellular growth/development, Elderly- related to accumulated damage, and failing immune and cellular repair mechanisms]
[I edited the entries above for improved clarity.]
Germline mutations. These are less common. A germline mutation occurs in a sperm cell or egg cell. It passes directly from a parent to a child at the time of conception. As the embryo grows into a baby, the mutation from the initial sperm or egg cell is copied into every cell within the body. Because the mutation affects reproductive cells, it can pass from generation to generation.
Cancer caused by germline mutations is called inherited cancer. It accounts for about 5% to 20% of all cancers."
I was told not hereditary as such but may run in some families more than others, my sister already had ET when i was diagnosed with PV and hers has progressed to show PV symptoms and more recent my mum has been showing mild PV symptoms.
I have PV. My first-cousin-once-removed had ET and it progressed to leukemia and he died. He was under 40. I'm 66. I know someone who has PV whose mother also had it. My father had Waldenstrom macroglobulinemia, a non-Hodgkin lymphoma, in which bone marrow produces too many abnormal white blood cells. Is there a connection? Who knows?
Despite MPNs not being hereditary, I am genuinely surprised by how many on this forum actually have more than one family member with an MPN, as we’re informed ‘familial clustering’ is rare.
Hi. That’s such a good question! My daughter was diagnosed with ET JAK2 positive nearly 20 years ago, then I was diagnosed with PV JAK2 positive 4 years ago. There are trials going on to see if there is what they call a familial tendency to MPNs. I’d love to know the outcome for the sake of my other daughters and grandchildren!!
At least there are ways of managing the conditions, but it’s still a concern.
Hi I have often wondered this myself. My late father had so many of the "symptoms" that I have with Jac2 Pos ET and am sure he must have had at least something like this.
I too make sure that I don't let this get me down and have always put a positive slant on the prognosis (apart from pure shock on diagnosis) and I can say that it doesn't affect my lifestyle in the slightest.
My father too of a heart attack,then all my cousins on my fathers side died of heart attacks well under 50 years old. They were all Jazz musicians ,the life style I always imagined being the thread.When I was Dx d here in France where I now live,the Medics at the hospital treating me asked why I had not been regularly checked with such a family history,heart ,arteries ,blood.
MPN's do run in some families and are comparatively widespread in certain population groups, especially Ashkenazi (Eastern European) Jews. They're so common here in Israel (for a "rare" disease) that even non-hematology nurses know the symptoms. In my case, no one in my direct family has an MPN. However, I personally know about 6 people, including a few neighbors, who have PV.
Similarly, mine thinks that a combo platter of daily X-ray exposures [ in my 7+ years working as an Interventional Radiology PA] and chemical exposures [3 summers in college spent working at Eastman Kodak- in a site that was declared to be an EPA Superfund [i.e., toxic waste hazard] site only decades later.- chiefly due to methylene and ethylene chloride, but including at least a few others.]
Perhaps ironically, my other medical diagnoses related to these exposure were evident long before the PV that brought me here.
The volatile organic compound [VOC] exposures in college led to eczema on my hands [and nowhere else- as we were told to wash our hands with them to reduce the risk of exposing plastic lenses to skin oils] and retinal changes [which were initially [mis]diagnosed as early macular degeneration in my early 30's], but which were luckily found to be stable changes noted to occur after VOC exposure.
The radiation exposure, during which I performed procedures daily using live fluoroscopy [despite religiously wearing my leaded vest, kilt, and thyroid shield] caused me to develop cataracts at age 50, when my parents [in their 80's] and siblings [2 older and 1 younger] never developed them.
Very good question! I have wondered this myself and as the other very good answer have stated there is no definitive answer (it seems to be mostly NO with some Yes). I have Et Jak2+ - my son has been complaining as of late (last 5-6 months) of aquatic pruritus after each shower - he is very red and itchy. He is 20 years old and while there can be various dermatological conditions that cause aquatic pruritus, it is a key symptom of MPNs (especially PV) - so at his next annual check up I am going to ask his doctor to do a full blood panel and see if I can convince him to test him for Jak2 while we are at it.....
I suspect that condition relates to the water. I stopped it happening after I moved away from the north of England. That was years ago, and I was only diagnosed with ET three years ago.
Hi there. I live in Michigan US. Diagnosed with ET or Primary Myleofibrosis ( BMB) also JAK 2 positive on Hydrea 1000 mg daily I am 65 years old diagnosed 5 years ago - Family of 8 my aunt who lives down street, my father and my brother all had myleofibrosis. Because they were diagnosed some time ago 30 years not sure if it started with ET and progressed. My brother who is 14 years older just passed on Easter of this year with myleofibrosis doctors say we were born with this mutation and that mutation was turned on in our lives by some exposure perhaps to benzene. We grew up on a farm non of my other siblings have this. I do know when I was about 2 I had to take iron bc I was very anemic. Our farm was downstream from a huge chemical plant Dow Corning which was known to have poisoned much of the Saginaw and Midland water and land with chemicals. So that is my theory is that we grew up poisoned. The Drs have told me not hereditary but they have seen it run in families probably due to some type of exposure that turned that mutation on. Good luck to you on this journey. I hope you find this helpful. God Bless.
Thank you so much for this detailed response. I'm so sorry to hear your story, I actually live very close to a petrol ( gas) station, so like you my gene may have been triggered.
from what I understand the ET is not hereditary. It’s an acquired gene mutation. I don’t think the science knows yet what actually causes it. Good luck.
I was diagnosed with ET ( with BMB) 2 years ago, age 51, now 53. It is now PV, Jak2+. Higher platelets for 16 years never diagnosed.
My now 21 year old has ET diagnosed a few months after me, BMB Jak2+ She takes 81 mg aspirin and and does blood tests every 6 months. She is doing great. Luckily the diagnosis helped her out when looking at regulating her cycle and future birth control as the pill would be out of the question.
I am on aspirin daily, Pegasys weekly, for the last 6 months. Doing great, no real complications platelets sitting at 326 🥳 as of a few days ago.
Get yourself an MPN specialist they really do understand more that most doctors and treat you as an individual.
Welcome to our worldwide club. Hope you feel a million times better once you understand and wrap your head around it all. ❤️
I come from a very large family and we are in our own club, no other family has anything so far.
Please help her to be assertive about advancing her treatment at the slightest provocation, because early treatment with IFN has been shown to be potentially disease-modifying [i.e., preventing progression to worse disease/outcomes].
Interferon-alpha in the Treatment of Essential Thrombocythemia
hey! I’m really interested in hearing more about your comment. What would you suggest as being a provocation in ET?
I have recently been diagnosed JAK2+ ET at 39 years. I also have family history of MPN and Leukaemia, tho my Haematologist was not super interested in that info as she said it’s not hereditary. I have a young family of 4 children and I want to be proactive in my treatment.
I was trying to be politically correct rather than coming across as a shill for IFN treatment, but given the positive findings with virtually all of the treatment trials, it's hard for me to stay noncommittal. Otherwise, I'd just have said- take any excuse to advocate for a switch to IFN.
As for myself, I was diagnosed w/ PV this past summer, and from April [when my PCP referred me to HemeOnc] onward, I stated spending hours looking online at professional medical resources for what the best treatment option[s] would be for me.
Despite [or maybe because of] my 'high-risk' status of being an ancient 63 y/o male [with mild osteoarthritis, allergies and no other systemic disease processes], which per my traditional [non-MPN specializing] Onc MD meant that I should take HU [and basically shut up about the long-term risks], I could not and still cannot understand why, if IFN is safe and well-tolerated enough for women of child-bearing age [which in medical speak means that they could be pregnant and not know it], and even pregnant women, it would be too hard for me to tolerate it.
Thus, I'm a strong proponent for IFN for most MPN's for patients that haven't failed a trial on it.
I'm just up to my 2nd dose of 100 mcg this week. Labs pending.
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