My original diagnosis in 2017 was ET triple negative. This diagnosis and ongoing treatment has been with haematology at my local hospital.
I recently, on request, had an appointment and blood tests with an MPN specialist. Blood tests show that I have CALR plus DNMT3A. Does anyone have any information and insight about this? My main questions are, Firstly, how could the CALR be missed in my original diagnosis? And secondly and more importantly, what does this mean, particularly the DNMT3A, in terms of risk and prognosis, in simple layman’s terms please? I’ve read a couple of papers and for a non-medical person they are not that understandable but seem a little worrying in terms of the DNMT3A?
I did ask these questions at my local team appointment this week, but the registrar, though lovely, had no idea.
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SuET2017
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Will you be having a follow up appointment with the MPN Specialist ? If so, these are questions you should be discussing with him/her.
I’m no medical expert, but maybe the CalR percentage was low enough to be not detected at the initial diagnosis. Is that possible I wonder?
Hopefully, more knowledgeable folk (EPGuy) can offer their input with regards to the DNMT3A mutation. ‘Layman’s terms’ is so important! I have read different things, so do not feel confident to comment. Nothing is straightforward in MPNs.
My name is Steve from Sydney, & I am Post ET / MF (CALR Type2), w/ ASXL1+ & VWS Type2
So, in the wash up, I have a couple of similarities to you...
Secondly, my guess is that when you were first Tested for an MPN, they only performed the standard test for JAK2, (this is not so unusual). It's also most important to recall that the main 'Driver' mutations, (JAK2, MPL & CALR Types), are relatively recent discoveries, and most of the medical fraternity is still catching up at this stage. (JAK2 - 2005; MPL 2005/6 & CALR 2013).
Your derring to a 2nd opinion w/ an MPN Specialist is likely why it was subsequently discovered that you had both a CALR (Driver), & the DNMT3A secondary genetic mutations.
Most of the literature that I have scanned thus far, would suggest that the DNMT3A mutation, when associated w/ CALR is quite rare.
On the one hand, having this DNMT3A mutation deserves further follow up from your MPN specialist, BUT pls... do not be surprised that most doctors will NOT be able to inform as to precisely what having this mutation will mean to your longer-term health etc...
I say this in all fairness to the medical fraternity, because there are often so many variables, which may mean that no-one could honestly say for certain (100% CI) exactly what your prognosis might prove to be... However, and all that said, your MPN Specialist should be where you should follow up, perhaps even pose the question to Prof. Claire Harrison?
In my own diagnosis (Dx), having the extra High Risk Mutation of ASXL1+, is believed to have a poorer prognosis risk assessment attached to it...
However, I try really hard to reduce my levels of bodily inflammation, by adhering to an anti-inflammatory diet and by exercising consistently. These days, I am 64, Dx 2016, I currently cycle distances of circa 200-300km per week...
... And if anything, in many ways, I am much fitter today than I was at Dx...
Papers/ peer-reviewed articles, are a tad harder to follow & understand, but I have found that they helped me remain relatively calmer in my mental / emotional response to my Dx.
Having a good MPN Specialist is a MUST for all MPN patients, in my view...
Hope this might have helped a little...
Best wishes
Steve
(Sydney)
PS. There are over 50+ different Types of CALR, your recent report should also illuminate you as to which one you have... Generally speaking, CALR mutations are more indolent than many of the alternatives, in my view...
Hi Steve, and thanks so much for the reply, it does help even if there are no conclusive answers. I hear what you are saying about the unknown and consequently uncertainty around MPNs and I am generally accepting of this and don’t really think about it too much, but this threw me off a little - it was a telephone call with Prof Harrison team and I wasn’t ready with questions. They did not say what type of CALR it is. I had guessed the pairing is rare from the literature as most discussJAK2 and DNMT3A and not much at all about CALR and DNMT3A. And Dr Google can be a bit of a scaremonger, which is why I generally avoid. I will go back to them though, as you say, there is unlikely to be the answers I’m looking for. I also now follow an anti inflammatory diet and keep relatively fit (good for you on the cycling, I’m more of a walker) both of which i believe make a huge difference to my fatigue levels. Cutting out sugar made a significant difference to me. And, as everyone says, drink plenty of water. Enjoy your cycle today and thanks again, sue
Yes, I know how easy it is to create unwanted anxiety about our MPNs. The ASXL1 mutation I have suggested that I would likely suffer sooner rather than later, (according to some, who are supposed to know more than me...
However, I am still here riding my own special MPN rollercoaster. I have some ups & downs, but mostly I am doing fine really. Many suffer much more acutely than me, that's certain.
Circa 80% of CALR Types are mainly between the Type 1 & Type 2 (Like) varieties.
Me (?), I am Type2, (acquired), which means in my case that it's also further complicated by Von Willebrands Syndrome (VWS – acquired Type2 also). It too is a rare condition. One minute my blood will be clotting very badly and the next I might be bleeding(?)
The other 20% or so CALR Types can also be rarer varieties due to one's personal body chemistry, as I understand it.
Nevertheless, I do believe that you should ascertain which CALR it is that you have.
Of the Type 1 & 2 Types:
My understanding, (& especially in my own case), Type2 is more likely to cause a Thrombotic event. I have already had possibly 3-4 Transient Ischemic Attacks - TIAs, (minor brain strokes). My Platelets usually range from low 700s to well over the 1M benchmark.
Type 1, in my own view, from the majority of the science that I have researched suggests that Type1 is most indolent in nature, where Thrombosis might be concerned...
However again, & just to further muddy the already sullied waters, "there is also some literature out there that suggests the converse to be true".
Of course, in my own experience, Type 2 is more Thrombotic & problematic... Of necessity, I watch my bloods somewhat closely from time to time, especially when needing to see a dentist. Bleeding gums has been a signature issue for me, & especially so when I was taking HU, less so now I'm on Ruxolitinib...
Anyways, best wishes & stay calm while learning more from your MPN specialist team. Remember Sue, always stay positive & looking for solutions... Life is just another problem waiting to be solved... ;-0)
I’m also acquired VWS, and tend to bruise and bleed a lot! Do you take aspirin? I have to monitor this, and if I take too much, I bruise and bleed more. However, I have no history of any clotting issues, which is a bonus.
Hi, I am 73 PV Jak2+ and DNMT3A positive with a 40% AB when tested 5 years ago. Every time I visit my MPN specialist I ask about the DNMT3A. So far, he always says that the significance is still not known. He tells me that there is no evidence so far that it contributes to progression and that studies of mutations that do lead to progression do not implicate the DNMT3A mutation. That's all I know. It seems to be a fairly common mutation as far as these mutations that they test for and they are not sure if it comes before or after the Jak2 mutation, I don't remember any mention of the DNMT3A combined with CALR. Let us know if you find any other information concerning the DNMT3A and MPN's.
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