As you may recall, my daughter is also JAK2v617f positive, currently showing as ET. My son has idiopathic erythrocytosis, no known mutation. My next younger brother was diagnosed with a high-grade Non-Hodgkin's B Cell lymphoma several years ago. Thankfully, his lymphoma was successfully treated with R-CHOP and surgery. My youngest brother was hospitalized last week with a spinal compression fracture/deteriorating bone structure in several lumbar vertebrae. The condition has spread to a femur. We just found out today that this is a Large B cell Lymphoma. He will be getting a spinal fusion in a few days to prevent the spine from collapsing any further. He will start R--CHOP a few days later. In investigating family history further, it turns out that there is a family history of blood cancers on my Mother's side of the family, including leukemia and lymphoma.
Based on what is in the literature, conversations with hematologists/oncologists and other doctors, and my own family history, I do believe that blood cancers can cluster in families. It is very important for the research in this area to move forward. This is something we can all contribute to. There are studies underway looking at the topic of these familial genetic links.
Here are couple of links.
Specific to Familial MPNs. My daughter and I are participating in this one.
I believe there is more research on the topic of Familial MPNs/blood cancers. I have seen reference to studies underway at The European Hematology Association, Mayo Clinic, MD Anderson, and NIH. I do not see links to any of these studies so do not know if they are currently active/recruiting.
Perhaps we can combine our knowledge and resources to come up with a list of other studies underway. Understanding the genetic links to a predisposition for blood cancers would benefit all of our families. We have the power to make a difference. We can help move the science forward through our advocacy and willingness to participate in the research.
Wishing all of you all the best.
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hunter5582
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Hunter, So sorry to hear your family is so significantly affected by these cancers. I have worked on my family ancestry and believe there maybe some connections we never will know. I appreciate your energy spent to our cause. I feel your persistence is helping so many you may never know. I had wanted to try and come to the August conference, but life sometimes has different plans for us. Hopefully 2025 will be less stressful, no more uninvited guests (Helene & Milton). Please stay strong, and prayers to you and your family. Christy
Hi Hunter, sorry to hear about your families history of blood cancer. My partners family are now part of a study in Oxford due to the JAK2 V617I mutation being detected in my daughter when she 1. He also has the same mutation and his mom and sister are now being tested. His moms sister has ET and his mom's mom also had thrombocytosis. Seems there could be a link on his moms side...
Sorry to hear that your partner's family also have the familial cluster. I suspect is more common than is recognized. Glad to hear they are participating in a study. If you can find a link to this study, please post it. Others will likely be interested.
Hunter I’m so sorry to read your family has a new challenge; you’ve had plenty of them already. Hope the R-CHOP is as successful as it was for your other brother.
You sound so balanced; it can’t always be easy to maintain. Thank you for your information shares. The thought of a familial element is daunting but awareness will keep us mindful of trends to be alert to in our families’ blood results.
So sorry to hear that your family has all these cancer issues. Thankfully, as far as I know and at the moment, other members of my family do not seem to be affected. Good to hear about the ongoing research in this area. We all do rely on and appreciate participants in these trials.
So sorry to hear of the issues affecting your family and sending good wishes for a successful outcome of your brother’s treatment and for you and the other members of your family.
Hunter, I'm so sorry to learn about your family's blood cancer cluster. My story is not as striking but still a bit suspicious. As you know, I was diagnosed with PV (JAK2v617f positive) back in 2015. One of my uncles (my mother's brother) was diagnosed with PV in the 1980s or even earlier; I know that his death in the late 1980s was due to a consequence of PV. My mother was never diagnosed with PV, but she dealt with serious vascular clots for many decades (including three months of bed confinement after the birth of her last child in 1950) that contributed to her death in 1998. Possibly a small familial cluster?
I would say that your family should also be considered a MPN cluster. Unfortunately, some people are never property diagnosed and MPNs go undetected and untreated. I expect there are more Familial MPN clusters than is commonly realized. Hopefully, as MPN diagnostics improve and we learn more about the genetics involved, more people will be properly diagnosed and treated.
Hey Steve... Seems that there is little doubt that a 'Familial' connection exists where your family is concerned... Most interesting too...
I recall quite some time back that I ran out that Question to many MPN Voice people, & as I recall, there was a great many with indirect / direct relations with a diverse array of blood & other cancers...
My own father had X 3 Remissions with Non-Hodgkins Lymphoma, he survived the treatment but his body, (which was once super fit), paid a heavy price for the chemo / radiation therapy etc.
He sadly went down quickly after a fall & his recent hip surgery (Hip- popping) experience left him for 36 hrs alone on the floor... Before his drop-in Nurse eventually found him...
Mentally, he never did recover... Few monthgs later he was gone...
Back to the familial connection tho' certainly appears to me that there are many people with a similar history to your own Steve...
Hunter, You are always so supportive and there for all of us, so sorry to hear about your family and your brother. I really hope they get the right treatments and do well. You will be able to support them with your knowledge but I hope you will take care of yourself too.
I think you are right about the family link . I have well managed ET but my father's family always had funny blood and anaemia. I am sure there is a link. Please keep us up to date with how you are all doing and know that we are here for you as you always are for us. Take care.
Sorry to hear about your brother and your children hunter .
I know my great grandmother had blood cancer on my mother's side , my mother was diagnosed with rheumatoid arthritis . My dad died at the age of 63 after having a heart attack aged 48 , throat cancer in his 50 and then a stroke at the 63 . I often wonder if my dad had PV , he died 30 years ago. Im not sure they knew about MPN back then or Jak 2 mutations .
I worry if my children could develop PV in later life , I was told my kids don't need to be tested .
I believe it is hereditary as well. My brother has Lymphoma, I have ET and now high iron levels in my blood, possibly Haemochromotosis. My sister said that my mother has the gene for Haemochromotosis. Several siblings have diabetes, so high iron levels must have damaged their pancreas. It is deglfinitely hereditary and clustering in families. Myself and my Mrs had several miscarriages and we are past the age now. I was sad at the time, but at least I'm not going to be passing this curse on to the next generation. Of that I am glad.
I am sorry to hear your family is having to deal with so many blood cancers.
There are some ongoing research projects in Europe about familial and hereditary cancers. My hematologist told me about one such study conducted in Uppsala, Sweden, on germline mutations in cancer. Part of a much larger study.
I am investigating now whether my ET is inherited, and it seems very much so. I will get a clear response in some months. Inherited ET can be often missed in previous generations, as it can be misdiagnosed as something else, and because it can be quite heterogeneous in symptoms and severity. Many doctors never heard of MPNs. In my case, the mutation seems to have been inherited from my father, who inherited it from his mother. I am the only one with an adequate diagnosis. They were misdiagnosed for decades, and my father was diagnosed, eventually, based on a BMB, but he already passed away when the results of the BMB came back.
Given how little known MPNs are outside university hospitals and academic medical centres, chances for people living in places with little access to specialist health care to get a diagnosis is low. And this was even more the case in the past. Probably this has contributed to the lower detection and little research on familial and inherited MPNs. Because from interactions in support groups, it seems that familial MPNs are not that rare. But everyone had to do detective work and put two and two together.
I assume we can also contribute to making this topic much more visible and raise awareness that this topic needs more research.
I lobbied for almost 3 years to get my mutation investigated as being germline. It was exhausting, to be honest, but I hope my efforts will make the medical journey of the people being diagnosed these days at the same hospital who also have a germline mutation easier.
There are several different ways that inheritance patterns may play a role.
One way is the JAK2 46/1 GGCC haplotype. This haplotype predisposes to acquiring the JAK2 mutation. Ther JAK haplotype can be inherited. This is what my daughter and I both tested positive for.
Another way is hereditary thrombocytosis (AKA familial thrombocytosis/familial thrombocythemia). This is a rare, autosomal dominant disorder caused by mutations in the thrombopoietin (TPO) gene or the thrombopoietin receptor (MPL) gene.
This is just a bit of what is in the literature regarding possible mechanisms for inheritance related thrombocytosis. There is also hereditary erythrocytosis as part of the possible patterns of inheritance. Better understanding the role of genetics in these disorders will help move the science forward, allowing for better diagnostics and hopefully better treatments.
Thank you, Hunter. I am quite familiar with the literature on hereditary thrombocytosis, as it was needed to advocate for my diagnosis. My mutation is MPL R102C.
I am not sure that familial thrombocytosis is synonymous with hereditary thrombocytosis. Familial thrombocytosis is an umbrella term, but from the literature the most frequent definition refers to the propensity to acquire a (pathogenic) somatic mutation than can cause ET/MPN during lifetime, while in hereditary thrombocytosis one is born with the pathogenic mutation that can cause the MPN, a mutation that one inherits from one of the parents and is present in the DNA of every cell in the body, not just in bone marrow and blood cells, like it is the case with somatic mutations involved in MPNs.
A more comprehensive list of germline mutations in MPNs can be found in this study:
There are also broader studies on germline mutations in cancer in general, and several germline mutations known to cause other types of cancer have been found to be able to cause MPNs too. These are rare cases, but the findings are consistent.
As my hematologist pointed out, these days is it very common to find what was before considered a rare mutation, because genetic tests have improved and so did the knowledge.
My daughter (aged 2) was found to have the v617i which is found to be a germline mutation from her dad as he also has PV. So now the rest of his family are being tested. Only the second family in the UK to have been recorded with this particular germline mutation however I wonder that alot of people are misdiagnosed as my partners initial diagnosis was Jak2 v617f, it was only when my daughter was also incidentally found with high platelets then a mutation after further tests that his diagnosis changed to v617i
Sorry to hear that this even more rare JAK2 variant is present in your family. The pediatric MPNs are a known issue, but much more needs to be understood about MPNs in children. Please let us know what your learn on this journey. Your knowledge will benefit others on the forum. Thank you for posting the link to the study.
Thankyou I will keep you updated, my 2 month old daughter was also tested yesterday so we will see what the results come back with. We've been advised she has a 50% chance of having it due to it being germline.
In my case, the first diagnosis read "ET with MPL mutation." And I was told I have a canonical MPL mutation at diagnosis.
But it didn't sound right, given the family history and the VAF%, so I asked for the results of the genetic tests and not only my MPL mutation was non-canonical, it was a germline mutation (inherited) and unlike the canonical MPL that is gain-of-function, my mutation was loss-of-function, but could cause hereditary thrombocytosis when heterozygous.
Someone else was complaining they were diagnosed with ET with MPL mutation, only to be reclassified as triple negative as their hematologist realised the MPL mutation the patient has is non-canonical, and instead of communicating that and spelling the correct mutation, they decided to ignore the non-canonical mutation. So the person is now worried and confused, and has to push to get their complete genetic results sent to them.
It seems like we need to fight for adequate diagnosis and this is not how health care should be.
Oh really how frustrating! it's crazy I never used to question medical things but when you go through this kind of stuff it really makes you more aware to try to be active about healthcare
First off, Im sorry to hear about what your family members are going through...also, I want to say that although I have been told by more than one GP that blood cancers are not inherited, I believe otherwise. My mom's father had leukemia and died in his mid 70's with it. My mother just died 4 years ago in her mid 60's ofCML (turned AML in the end) and I have ET - since I turned 40. I am certain that it is not just a coincidence. I'd like to understand more if it is familial or if there is an environmental factor involved. I was born and raised in the wheat belt of Canada and have been told casually once that the highest incidence of blood cancers are in thos region? So that is a consideration too
Sorry to hear that this clustering of blood cancers has impacted your family too. The answer is most likely that cancers are the result of both genetic predispositions and environmental exposures.
Our friends at MPN Advocacy and Education International are advocating for recognition of the link between MPNs and environmental exposures experienced by our veterans. Unfortunately, the VA does not currently recognize this, mpnadvocacy.com/?s=veteran
Thank you for bringing this important topic to light. I am sorry that your family is also going through various forms of blood cancers. Despite it all, you still are always willing to assist others on their MPN journey, and I thank you for your dedication to this forum.
For those of us who have a familial clustering of blood cancers, it is very important to look into the possible reasons why and be tested, if able. As you have shown, there are a few cancer research centers that are testing those of us with familial clustering, usually at no cost to us, to assist in this vital research.
I also have a clustering in my family. My younger sister (at age 48) and I (at age 53) were both diagnosed with PV Jak2+ only back in 2014 . Our mother was diagnosed with ET CALR+ in 2016 (at age 84). Our Mom is doing well at the age of 92 now, only on a statin and low dose aspirin!
Last year, our niece (our brother's daugher) was diagnosed with both PV and Hemochromatosis at the age of 42. We also have a first cousin who has Multiple Myeloma, who had a SCT 2 years ago and is stable at this time.
My sister, myself and our Mom participated in Dr. Angela Fleishman's Familial MPN study at UC Irvine, CA (sending our blood and nail clippings through the mail as we all live in upstate NY). This was back before the pandemic hit our world, so when trying to get any results of our tests, labs were shut down only for Covid research. Even to this day, we still have not received information regarding the research performed on our blood and nails. I know this research project is continuing though.
I regularly see a local hematologist, however, Dr. Raajit Rampal at Memorial Sloan Kettering Cancer Center in NYC is my MPN specialist since the time I was diagnosed with PV. I had a VAF and NGS performed locally last year, which showed my Jak2 VAF at 55% with an additional TET2 mutation of 2%. I have been taking HU (hydroxyurea) at increasing dosage since diagnosis in 2014 as I had a very high symptom burden at diagnosis. I have since had 3 superficial blood clots following a surgical procedure in 2022. Dr. Rampal recently wanted me to participate in the MSK IMPACT/Heme genomic research project due to the clustering in my family. It tests over 400 genes for cancer.
The genetic specialist I had spoken with at MSK mentioned that if I had a germline familial MPN, there would be a SNP (snip) on my DNA testing from my nails. I spoke with Dr. Rampal yesterday as my results revealed that besides my somatic driver mutation for PV (Jak2V617F) at 58%, I also have 3 additional somatic non-driver mutations of TET2 at 5.6%, DMNT3A at 4%, and SH2B3 mutation at 2.2%.
I do have a germline mutation, NBN, of which I am a recessive gene carrier, which can cause Nimegen breakage syndrome, or has been seen in other cancers including blood. Therefore, without the germline SNP for a familial MPN, it appears I cannot pass it down to my children. (This may be why I have never heard anything from Dr. Fleishman regarding my germline tests performed back then??).
However, my mother, sister and I were exposed for many years to National Lead Industries in NY, which had been putting out depleted uranium in the air through smoke stacks, so that may be a cause from the environmental conditions we were exposed to for at least 20 years. We found this out after we were diagnosed, as we had since moved from the area of the plant and the federal government had begun a clean up of this site, which took 3 decades. The plant was ordered to shut down in 1984. The DOH offered testing of those who lived near the plant in 2012, which we were unaware of until after we were diagnosed in 2014, as I began researching what could have caused my sister and I to develop this rare blood cancer within months of each other.
Despite my high Jak2 VAF, I have been very stable with all of my blood lines, except my platelets, which run in the 6-700's, but thankfully I am basically asymptomatic & those numbers are currently not recognized as a thrombotic risk in PV. I have had no bleeding issues either. I stay very active, have very little fatigue, recently climbed 7.5 mile roundtrip mountain hike in Acadia National Park in Maine and have not had a phlebotomy in over 2 years. My concern was my high VAF, and a possible potential for progression, but since I have the DNMT3A mutation, that makes me a poor candidate for interferons and at this point, besides a high VAF, the new mutations are not high risk for progression to Myelofibrosis or AML, so we will not make treatment changes unless things change symptomatically since there is still not much data that shows a higher VAF means worse prognosis (AT THIS POINT). Jakafi would be my next treatment option, especially if the data continues to show a decrease in VAF with this treatment or I become symptomatic of any kind.
I feel as you do that there is importance to being part of these research studies, which our MPN specialists offer, to possibly provide more answers down the road. Thanks again for all of the support provided on this forum.
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ET cancer or not.
Blood cancer uk research
Jak2 Neg, ? Familial PV
