New mutation

[Graham7694]

Morning all

I haven’t posted for a while as have been struggling along nicely on peg ......

My platelets have remained steady although my HCT has been creeping up. My specialist arranged a red cell mass scan and my red volume is normal so he is not too concerned about HCT being raised.

The letter from my last appointment has come through and I am a bit surprised to note a new mutation

Framework mutation ASXL1?

Should I be concerned?

No mention of this before

Regards

Graham

[socrates_8]

Hey Graham...

My name is Steve from Sydney... Happier New Year's greetings buddy to you & yours... and for everyone one us globally... What a year it has been... Hopefully, we are always moving towards happier times in 2021...

Graham, I am happy to try to share whatever MPN information I might have with you, however, it would also help to know a little more about you first, (meaning all of your associated MPN variables etc...)

For instance, I am 61 yo, diagnosed 2016 w/ Post ET / MF. My 'Driver' mutation is CALR+ Type2, and I also have ASXL1+, and Von Willebrands Syndrome, (VWS). Over the course of my MPN journey thus far, there have been a few changes, for e.g. My Bone Marrow Biopsy (BMB) results improved from Level 2 down to Level1. I like to believe because of my diet & exercise regime all helping to reduce my "Inflammation" over time... ~ however, I might be mistaken, as I often am... ?

Graham, which MPN, Driver Mutation, and other potentially adverse High Molecular Risk (HMR) mutations might you have?

Answering whether or not you need be concerned or not, will largely depend upon first answering a few other pertinent questions too I am afraid... For while many of us might have some similarities in the flavour of our MPNs, none of us will be exactly quite the same, in my view...

While the information provided below is general in nature only, it may assist you a little. However, please always only follow the advice of your medical team / doctors, and they should also be able to help you understand what "Frameshift Mutations" like ASXL1 are etc.

It can take some time to learn about our MPNs. However, here below are a few links that might help a tad in the mean time...

* mpn-mate.com/mpns-what-are-...

* mpn-mate.com/essential-thro...

* mpn-mate.com/polycythaemia-...

* mpn-mate.com/primary-myelof...

Hope something here might help understand a little more about MPNs

Best wishes

Steve

[Graham7694]

Hi Steve

We have spoken in the past

My current diagnosis is ET with CALR type 1 and ASXL1 mutation

I was originally diagnosed MF and was started on ruxolitinib but this changed to ET following a second BMB and then moved to Peg

The ASXL1 is a new bit to the diagnosis and follows NGS testing

Hope this makes things a little clearer

[Aneliv9 in reply to Graham7694]

So did you have an MF diagnosis during your first BMB that then changed ???

[Graham7694 in reply to Aneliv9]

Yes - my original diagnosis was MF following my first BMB. I went for a second opinion at a different hospital and had another BMB where the diagnosis was changed

[Aneliv9 in reply to Graham7694]

Oh i see.... So your first diagnosis was wrong.

[socrates_8 in reply to Graham7694]

Hi again Graham...

Apologies about my delay, I've not been terribly well of late... & hopefully on the mend now...

I believe I do recall we had a chat quite some time ago too...

Graham, I would quiz your doctor on the ASXL1 because it is mutation that is generally considered as having an adverse impact. However, you didn't mention if the ASXL1 was Positive or Negative(?) That is also an important piece of the puzzle too... so please ask them (your MPN Specialist), what they have to say about it.

I was diagnosed in 2016 with ASXL1+ and I am still here, and we have some similarities in that I am Post ET /MF w/ CALR+ Type2 (whereas you are Type1)

It is also my understanding that CALR Type1 like mutations are supposed to be more indolent than Type2 mutations, (that is just based on my general knowledge from reading peer-reviewed Papers etc)

However, always best to ask your specialist... BTW, is your Specialist an MPN specialist?

If not, perhaps your might try to find one over there... You definitely have a slightly larger pool of MPN doctors than we do here in Oz, as I understand things at the present.

Best wishes Graham...

Stay safe & well buddy...

Steve

[hunter5582]

ASXL1 is one of the non-driver mutations associated with MPNs. The short version is that it increases the probability of disease progression, but not mean that it will happen. It is relevant to the monitoring and treatment of your MPN.

Here are a few links to info about ASXL1 and MPNs

nature.com/articles/leu201069

ashpublications.org/blood/a...

ashpublications.org/blood/a...

The term "frameshift" refers to one of the four types of genetic mutations: transition, transversion, deletion, insertion. "A frameshift mutation (also called a framing error or a reading frame shift) is a genetic mutation caused by indels (insertions or deletions) of a number of nucleotides in a DNA sequence that is not divisible by three." Wikipedia

A bit on this topic www2.csudh.edu/nsturm/CHEMX...

Do be sure to pay attention to the erythrocytosis. Masked PV is often misdiagnosed as ET. That did in fact happen to me. I had ET which progressed at some point to PV (approx 7 years ago). My old hematologist missed the progression and was not treating the MPN correctly. This lead to me discovering how common it is for hematologists to have little/no experience in treating MPNs. I now consult with a MPN Specialist. Here is a link to a list of MPN-expert docs mpnforum.com/list-hem./ .

As Socrates_8 indicates, the answer to whether you should be concerned depends on a number of factors. MPNs are complex disorders and we are each different in how our MPN presents. As Socrates indicates, this is a question that you need to review with your care team, which I hope includes a true MPN-Specialist. Suggest learning a bit more about the CALR and ASXL1 mutations and the role they play in MPNs. Socrates provided you with some links that will be helpful in learning a bit more about MPNs, which is also important. By the time of your next appointment with your hematology team, you may have some much more specific and informed questions to review.

Meanwhile, suggest that you do have a reason to be concerned, but not excessively worried. You are already on PEG-IFN which current research indicates is likely the best choice to prevent disease progression. Knowing you have the additional mutation does not change that it has been there all along. The only thing I would add is that it supports the importance of making good health choices: diet, exercise, healthy weight, avoiding toxins, etc.

All the best to you.