I wanted to see if there are other people out there who have been diagnosed with essential thrombocythemia with non-canonical MPL mutation.
Mine is MPL R102C, it is very rare and in my case it seems to be hereditary.
And if you have been diagnosed, for how long have you been having essential thrombocythemia and what are your symptoms?
I know from support groups that people with MPL mutation are often undertreated and often experiencing more fatigue, but as there are very few people, it is hard to know if there are people with non-canonical mutations.
You can read here about what mutations are considered non-canonical and germline:
This is a summary of non-canonical mutations and why this interests me:
I was just curious to see whether people get tested for a broader range of MPL mutations. Mine is a non-canonical loss-of-function mutation and I wonder if there is someone else out there with a similar mutation. There are many MPL pathogenic mutations, some canonical, some non-canonical.
For hereditary ET, germline mutations can be: MPL K39N; MPL R102C, MPL R102P, MPL R106L, MPL R120W, MPL R170H, MPL V501A, MPL S505N and MPL W515R.
There are other papers on both germline and somatic mutations that are non-canonical (often found in patients initially considered triple negative) and could be involved in ET and PMF:
More interestingly, some mutations are seen as activating mutations:
"we showed that L498W is an activating mutation potentiated by H499C and that H499C and H499Y enhance the activity of the canonical S505N mutation. L498W and H499C can activate a truncated TpoR mutant, which lacks the extracellular domain, indicating these mutations act on the transmembrane (TM) cytosolic domain."
Hi! I have ET with MPL driver, diagnosed in Nov 2021 by BMB. My platelets were 1150 and I had chronic fatigue, constant headache, pain in my big toes, bouts of itchiness, night sweats and visual occasional floaters. In fact, all the symptoms associated with ET. I take daily aspirin and Hydrea - 4 days x 500, 3 days x 1000. Platelets now about 450 and most symptoms reduced apart from bouts of fatigue. I had no idea that there were so many types of MPL! My next review is in June- I’ll ask if they know!
just looked up my MPL mutation and this is what it says
MPL: exon 10, c.1544G>T p.(Trp515Leu), VAF 32%
NM_005373.2, rs121913615, COSM18918. Don’t know why this is underlined
I was diagnosed in 2010. Initially has toe pain +++ this stoped once Istated aspirin. Also got burning feet.also stopped with aspirin. . Been on Peg interferon 2 years. Never used to get fatigue but do now especially on the days I work
This variant seems to be somatic, so most likely it will not be inherited by the children of people who have it. Sometimes one can inherit a predisposition to acquire a somatic mutation on genes related to MPNs, those are called familial MPNs. This is an interesting case study on a family with familial essential thrombocythemia:
Just keeping an eye on blood counts is a good strategy.
And it seems like there are some initiatives now to invest in finding treatment that can not only prevent thrombosis, but that can prevent or stop disease progression. One can only hope for targeted treatment for ET in the future.
Either way, even if someone inherited a mutation from their parent, it is not the parent's fault.
I have inherited my mutation from my dad who inherited it from his mom. I do not blame them, this is how it is. In a way it is easier for me as I saw how illness was for them, although granny was left without an official diagnosis and my dad got his after he passed away.
I was diagnosed with ET MPL last year so am very new to this. I am on hydroxycarbimide tabs which are keeping my platelets in the normal range… muscle and joint pain, also a small degree of fatigue. Was told it’s not herediarry and cant pass on. Your post is of interest to me…. But really couldnt continue with what you wrote as went over my head🥴
I am glad for the posts in this group. Until I started reading here,I was baffled at the constant headache ( two years of it),so tired that I would sleep two to 4 hours in the afternoon along with the spinal pain from scoliosis ( back and neck) long bone pain in my left leg. I hope this doesn't sound like I am complaining. I am great full that at 70 I can still do what I have done for 47 years. It's the brain fog that to me is bad at the moment. I quit taking the hydroxurea, it made me so sick I couldn't work. My platelets have increased to 757,000 so I am weighing out starting back on it . Any advice?
Hey there! I have a canonical MPL mutation (W515K).
Prior to diagnosis (late 2022) I'd occasionally have night sweats (though debatable whether truly from the MPN or the temperature in my room/my bedding) and had scintillating scotomas a handful of times. I've had migraines since my late teens and didn't necessarily notice any changes there.
As far as the fatigue question, I definitely do have days where I seem more fatigued/tired than usual. But, I also have a demanding full time job (with long and at times erratic hours), 2 young sons, and don't often get enough sleep. All to say, it's hard to know if it's the MPN or the circumstances of my life causing the fatigue!
Currently on aspirin only. Hoping for a cure for us all soon. (And until then, better medicines to help us all to lead healthy lives.) Always grateful to all the physicians/scientists working towards those goals.
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