Finally, a clear diagnosis

[TTA_]

I was diagnosed with essential thrombocythemia in 2020. Although my platelets have been elevated since I can remember, and my father passed away due to what seems to have been high-risk myelofibrosis at age 62, it took a while to convince my hematologists to test whether the mutation I have is inherited. The results are in and my mutation, MPL R102C, is germline, it is inherited. So now my diagnosis was changed from essential thrombocythemia to hereditary thrombocytosis.

I received the whole "as there is no clone, HT strictly does not enter into the chronic blood cancer category," and I held my ground and mentioned that the mutation I have has the same effects on my body as any sporadic mutation that results in ET would have: increased number of platelets, dysfunctional platelets, risk for clotting and bleeding, risk for transformation in MF, etc. So while this diagnosis means that, sadly, there is no treatment for me other than aspirin, the effects HT has are the same as ET. And that I do not want to fall through the chairs because at the moment there is no treatment for HT and that not much is known about the mutation I have.

My hematologist is OK and well informed, so I am lucky in that way. I just want to make sure I push as much as I can for better research and better knowledge about hereditary thrombocytosis (HT).

[PeaceXO]

Sorry to hear they won't treat you the same as if you had ET that's not fair as like you say it carries the exact same risks only difference really is that you were born with it and it wasn't acquired. As you might remember my partner also has a germline mutation: jak2 v617i . So it's interesting to speak to someone else with HT as that's what my daughters diagnosis is. It doesn't show on her letters from the childrens hospital as MPN or ET even though her platelets are 867 on the last test and has a jak2 mutation. I'm not sure whether that will change after a BMB though...

[TTA_ in reply to PeaceXO]

Hopefully, the doctors will give your daughter the correct diagnosis and will do an adequate monitoring and, with some luck, your family (partner and children) will be included in a study. Because that is the way forward, both for learning more about the mutation, and for efforts for a treatment to be found. I hope your children grow without being affected too much by the higher level of platelets and that they can grow into happy and accomplished adults. And, in time, we can hope for something close to a cure.I am fighting to be included in studies and to raise awareness about hereditary MPNs. I was so very lucky to not have had serious issues throughout my childhood and adolescence, except for some bleeding episodes, because there was no diagnosis and no treatment, high platelets were blamed on iron deficit, growing up, etc. I do not want another child to pass through that.

[PeaceXO in reply to TTA_]

Thankyou that means alot, they are in a study now already so hopefully that will bring something to light! I'm so glad you are trying to raise awareness for this as well I think so many cases are hereditary that aren't known about. We were told when my partner was initially diagnosed it's not hereditary and he was told he had the jak2 v617F.. we then found out my daughter had it & the diagnosis changed from the F mutation to the I mutation.. turns out his mom and aunt also have it and it's germline.. alot more research is definitely needed in the subject.

[hunter5582]

I am glad to hear you have a definitive diagnosis. I do not know much about HT. My understanding is that it is only high-risk cases that get recommended for cytoreduction. Please do keep us informed on how things go in your case and what you learn. We can all benefit from your knowledge.

[TTA_ in reply to hunter5582]

Hi, Hunter!

I hope all is well with you.

According to my hematologist, who explored the scientific literature on current treatments for HT and what could benefit HT patients, cytoreduction is not recommended for HT patients, as cytoreduction is based on ET/PV, where there is a clone. As that is not the case in HT, where the mutated gene is in every single cell of the body, not just blood and bone marrow cells, as long as HT doesn't transform (because HT can and does transform, despite myths that it doesn't, studies show transformations), the only recommended treatment is small dose of aspirin. For the rest, only focus on treating individual symptoms.

Apparently, more research is done now to understand germline mutations, especially THPO, MPL and JAK2 germline mutations. My hematologist hopes for better knowledge in 5 years from now. I hope my HT stays calm in the next 5 years.

[PeaceXO in reply to TTA_]

Hi again yes you're right it does transform, my partners germline jak2 mutation has transformed to PV from HT so futher proof it does

[Fairydust1111]

I was diagnosed with ET with mpl mutation in Ireland in 2023 and have been told by my consultant and experts at mpn forums which I have attended that ET is not hereditary. What you have posted is enlightening and makes me wonder…. Thank you and wishing you good health always

[ETinNYC in reply to Fairydust1111]

I believe it depends on the type of MPL mutation you have. Do you know which one you have? Most common ones are the MPL W515L and W515K. These are not hereditary, as per my MPN specialist.

[Fairydust1111 in reply to ETinNYC]

Thank you kindly for that information, appreciated. I was simply told that I had ET with MPL….. will show your info to my consultant this coming Wednesday at my appointment and see what he says 🙏🤗

[TTA_ in reply to Fairydust1111]

I was also told that I have ET with MPL mutation and that the disease is not inherited at the beginning, when I received my diagnosis. I mentioned my dad passed away from what it looked like a sort of blood cancer (later it became clear it was high-risk myelofibrosis). I was tested for genes for leukemia after I gave that information, luckily I had no pathogenic mutations there, but my diagnosis remained ET and no further investigations about inheritance were done. Over time, I gained some courage and asked for the report on the exact MPL pathogenic mutation I had, I received the report and I had to translate the name of the pathogenic mutation to its short form, which is MPL R102C.

3 years into my diagnosis I was so confident my thrombocytosis is inherited, that I asked for a second genetic test on my mutation. I was lucky, because the geneticist mentioned in the report that this mutation is germline, thus it is likely inherited, and appended a study showing it was inherited.

In the scientific literature, there was little information on the mutation I had related to ET, as mine was heterozygous, and studies showed the homozygous MPL R102C is linked to CAMT. But a study from 2017 showed that in its heterozygous form, MPL R102C is linked to hereditary thrombocytosis. I checked again and more recent studies support this. So for about two years I pushed my specialists until one listened and decided to check if my mutation is germline (this means that it is present not only in blood and bone marrow cells, like somatic mutations, but it is present in every single cell of my body, hair, nails and skin included).

I wonder how many people are told they have one MPL mutation, but never told if it is canonical (MPL 515K/L/R/A, i.e., exon 10 mutations) or non-canonical, or if it is somatic or germline. MPL S505N is hereditary and these days seen as canonical mutation (exon 10 mutations), for example.

If you have the energy, it is worth it to know exactly what mutation you have. In the end, it is a right of yours to get the information you need. I wouldn't worry much about what studies in the scientific literature say about transformation based on mutation type, because the scientific literature on MPL mutations is not stellar and many studies have small biased samples.

[Fairydust1111 in reply to TTA_]

Thank you so much TTA for your very comprehensive and lengthy reply, much appreciated. I have family coming today as is my son’s birthday but will read, digest and reply to you this evening ( irish time)🙏🤗

[Fairydust1111 in reply to Fairydust1111]

Just getting back to you now, sorry. I have a consultation with my consultant this Wednesday TTA, would you mind if I show him what you wrote to me and ask his opinion? Please let me know. The info you gave me is cery detailed but being 69 years yound some of the terminology goes over my head

Late here in Ireland so off to bed. Your communication is SO much appreciated 🙏🤗

[TTA_ in reply to Fairydust1111]

Of course, use the information. If you want some studies to show to your specialist, I can send them to you. I wish you a productive and helpful consultation with your doctor. If they give you the mutation in the long form, or tell you they do not know the short name of it because it is in the long form (includes where the change happens), ask them to give you the genetic report anyway and I can help you with the short name of the mutation.

[Fairydust1111 in reply to TTA_]

Thank you so much, you are so kind. I will get back to you after my consultation on Wednesday . Until then, stay safe, healthy and ….. happy🤗

[Fairydust1111 in reply to TTA_]

I am so sorry TTA am just getting back to you now apologies. I went to my consultation last Wednesday atemed with the information you gave me but the waiting room was full and I was not seen at all. After 2 hours waiting due to backlog of patients, mt consultant in passing said Maura go home….I will call you before the weekend…. He never did… I rang the hospital to be told that he is now on vacatation🙄🥴🤗🥴

[TTA_ in reply to Fairydust1111]

I am so sorry your consultant was too busy to see you and then did not call you at all. They are rather disrespectful. I hope they will compensate for this, as your time is also precious and keeping you waiting and never getting back to you is not a show of professionalism.

Many hugs of support 🌷

[Fairydust1111 in reply to TTA_]

Thank you, and to you too🤗🙏

[Tipsy2023]

Morning I can only applaud your perseverance. Having at least a clear diagnosis really does help and standing your ground is not easy . I am still on that road .L

[TTA_ in reply to Tipsy2023]

Good luck! I hope you find/have a good specialist who listens to you and who is willing to help you learn more about your illness.

[MaggieSylvie]

That's interesting. I was diagnosed with MDS/thrombocytosis, which is very confusing when everyone is talking about ET. I would love it if someone would enlighten me. The other thing is that some of us don't have parents any longer, and I have no children, so we cannot know whether it's heredited or not. I have no mutated genes either, and it's just aspirin and watch and wait, as well as Epoitin for the MDS.

[TTA_ in reply to MaggieSylvie]

I am sorry you are left without better answers by your doctors. Your situation is quite complex. It is not that difficult to find out if you have non-canonical mutations, for thrombocytosis. Your MPN specialist just needs to test you with a broader genetic panel, that explores the entire JAK2 and MPL genes, as well as non-driver mutations, not just the parts of the genes where canonical mutations are located. My hematologist told me this too, that many patients who were considered having no genetic mutation were found to have mutations with broader panels. Regarding knowing if your mutation is germline, once you have a pathogenic mutation identified, that is not that difficult. You need to test the DNA of cells that are not blood or bone marrow cells, such as skin or nails. Sporadic mutations, i.e., the mutations we acquire during lifetime and that are the most frequent mutations causing MPNs, can be found only in blood and bone marrow cells. Germline mutations, inherited mutations, can be found in the DNA of every single cell in your body.

Many hugs of support 🫂

[MaggieSylvie in reply to TTA_]

Thank you, TTA. I don't think I even have time for all of that, when I'm feeling quite well. My main issues are seven compression fractures. I can feel them, when I can't feel blood issues. These days I'm not even getting out of breath so much with the pain - just a bit "groany".

Hugs back to you. Thank you🤗

[RoundTheWorld]

Thanks for sharing. Well done for persevering and getting a clear diagnosis now. Hope the studies progress understanding of and treatments for HT soon.

[johnnyjumpups]

TTA, you have been so helpful to so many people in this community. I am very happy that you have found your answer, but sad that they have no treatment for you. You are such a kind and compassionate person, and extremely intelligent. You have given such valuable advice and information to us here and on other forums. Don't stop digging for your treatment. If anybody can find it, I think you can! I am hopeful for you!

[ETinNYC]

Just wanted to applaud you for not only advocating for yourself and getting a diagnosis, but also for your willingness to push for being included in studies and your desire to further the understanding and science around HT. I have a canonical MPL mutation and my MPN specialist also said there is more work happening around THPO and MPL. I hope as a result, it helps to shed more light on our conditions and hopefully better treatments.

Wishing you the best. Big hugs from NYC.