I have pmf-MF with JAK2 mutation and have been taking Rux since the end of 2018. Currently, Rux is took in combination with interferon. From the biopsy and blood routine, I have now reversed to PV (Hemoglobin has significantly improved, and the size of spleen has also shrunk a lot, although it is still quite large compared to normal people. After all, when I was diagnosed, I had a huge spleen, and my left side of abdomen was full of spleen).
But, I don't know from which year I discovered that I have the ASXL1 mutation, which has a poor prognosis, and currently there are no any drugs available, so I can only let it develop.
I have studied this disease very deeply, in order to better manage myself, but for this ASXL1 gene, it will eventually lead to the disease entering the acute phase, eventually leading to MDS and leukemia. If the mutation rate is higher than 20%, it indicates that it is not good.
Now, I am in the danger phase because of the mutation rate. I live a worried life every day, knowing what my future holds but powerless. 😭I am very afraid of stem cell transplantation because it is gambling and I do not have a suitable donor.
I also search for information and research everywhere. I heard that there is an inhibitor called BAP1 inhibitor, but it may still be in the development stage. At least as a patient, you have no way to obtain this medicine. And I don't know if this medicine is really effective for ASXL1.
What should I do😭I am only 37 years old. 😭😭
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merlisa
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While you are correct to think that having the ASXL1 mutation in addition to the JAK2 mutation increases your risk of progression into blast phase/AML, it is not correct to think that this non-driver mutation ensures that will happen. It is a matter of increased probability not of certainty. I am in a similar situation. I have the NF1 mutation in addition to JAK2, which increases my risk of progression to AML.
You indicate that your treatment regimen resulting in reverting to PV from pre-MF. This is a very good sign regarding your prognosis. Most people do not progress directly to AML from PV. The disease usually progresses through MF before reaching AML.
I am not familiar with BAP1 inhibitors. I believe you are correct that there are some of these agents in clinical trials, but I do not know of any related to MPNs. Please do let us know what you learn.
The "what to do" question is one many of us face. We all do eventually, regardless of having a MPN. While the NF1 mutation is less a risk than ASXL1, it does create another disease, Neurofibromatosis Type 1. This is what caused the brain tumor I had to have resected. When I found out the ET had progressed to PV and had to have heart and brain surgeries all in the same year (June 2018-June 2019), I found I needed to think through how I would manage. This is what I came to.
I understand that the MPN risk calculations show statistical projections, not an individual prognosis that determines my lifespan. I have no plans to die on a schedule. There is no MPN timeclock ticking away in my body. It does not matter what the statistical projection of my lifespan is. I plan to remain focused on living a good life for however long that is possible. Treatment options have improved and are continuing to improve. Perhaps there will be something curative in my lifespan. I have plenty left to do and enjoy in this life and plan to stick around for as long as I have a decent quality of life.
I start every day with the Serenity Prayer and embrace its meaning. I endeavor to remain focused on the things that I can control and let go of the rest. I seek to enjoy each and every day. I do what I can to ensure my health and work to ensure my quality of life.
Wishing you peace and success moving forward on managing the MPN.
You are on what many experts and members here consider the best therapy we can get, IFN with Rux. Your reverting to PV is a great sign it is working.
Are you checking Nucleated Red Blood Cells (NRBCs) levels?
On the SCT donor match, there is my take on talk from Dr. James Rossetti in a post last year
"They can now manipulate donor cells so it's easier to find a match. Donors no longer need to be as close a match as before so near all can find a donor."
Have you asked your Drs about how they are searching for donors?
BAP1 is also new to me. I looked into it briefly. You have found an interesting area of research.
You may be referring to this report or others by these authors:
"To test this hypothesis, we first examined whether deleting one Bap1 allele can delay or even eradicate ASXL1"
From other reports I came across BAP1 has been associated with either of suppression or promotion of tumors as the present report notes:
" This study discloses, for the first time, that BAP1 may represent a “double-edged sword” in cancer." ... "This study uncovers an unexpected oncogenic effect of increased BAP1 activity resulting from truncation of ASXL1 in leukemogenesis"
If so it points to BAP1 favoring the selection of the truncated ASXL1 form, this being the one related to leukemic transformation.
I can't find that they answered their 1st question, as you also note. In general this area shares with many others being in early phases. But that there may be this option is encouraging.
--
Anyway at least in the US BAP1-i's seem not in clinical use yet:
"BAP1-IN-1 (Compound 8) is a BRCA1 associated protein 1 (BAP1) catalytic activity inhibitor"
"For research use only. We do not sell to patients."
You are also a very professional patient. Thank you for your literatures and materials, which helped me understand better. I hope I can benefit from them. Hope that we can all live well and enjoy every beautiful day.
Reversal result is got through biopsy. I usually undergo a bone biopsy once a year, and my biopsy has shown reversal for several consecutive years. From the peripheral blood count, it is true that my hemoglobin level is much better than when I first started taking Rux.
Yes, I have the records on the Nucleated Red Blood Cells (NRBCs), very very low, around 1-2%. indeed, the result is exciting. But I have always been worried about my future percentage of blast cells.
I too can understand your feelings of anxiety... However, Hunter makes some great points that I agree w/ completely... We really MUST stay positive in our journey's & simply continue to live the best lives we can, while we can...
I am Post ET / MF, & I too am ASXL1+...
Yet, w/ my change of life-style, anti-inflammatory diet, cycling exercise & my positive attitude, I too am still here after being diagnosed (Dx) in 2016.
It's also a great positive that you have reversed your illness using "Ruxo-Peg" I am guessing...
And hopefully, your spleen will continue to reduce in size...
In Sydney, Australia, where I am from... I started our own MPN Patient's Forum, which later became registered as an Australian NFP Charity, that specifically raises funds for research into MPNs...
We don't raise huge amounts, however, we have turned this negative into a Positive, and personally I gain much strength & support from attempting to do so...
Hopefully, into the future, there may soon be other discoveries that can help MPN patients live more normal lives...
And as Hunter mentions above... There are NO Guarantees that even w/ ASXL1, that it will cause a fatal mutation that shall hasten my demise...
I am also keenly hearing your thoughts concerning ASCT... I also share something in common w/ you there that I too do not have a 10/10 "sibling" match...
However, science & nature can often be magical things... So I just keep my ear to the ground & keep watching that space for future improvements too... There are a great many inspirational MPN stories out there... Hunter's is certainly one of those, but there are a great many others too...
Remembering always that the "Driver" mutations of MPNs were only really relatively recently uncovered since 2005–2013, and much has improved in MPN treatments because of that... In other words, research is still in an early phase atm, in my view...
I too at first allowed the sword of Damocles (metaphor for presence of ASXL1) dangling above my thoughts to disturb me... However, these days... I hardly remember its there at all, until its mentioned in conversation...
You, like Hunter, can give me hope when I am most helpless and confused. Thank you for your suggestions. Can you share the anti-inflammatory diet you mentioned? Indeed, I also need it, especially in recent years when I have gained a lot of weight.
There are no general diets, you must personalize it according to your genes. And, taking care of your microbiote where immune system, 80%almost, is reguleted, helps. Changing the lifestyle to another healthy, is the way.
I'm sure you're a very determined person. As an ordinary person, I may not have cigarettes or alcohol, but there's less sugar and beverages, mainly because beverages also contain a lot of sugar that is hard for me. This is too difficult. I need to gradually develop a habit of eating less carbohydrate and more high protein. Thank you for your suggestion. I will try to adapt to a healthier lifestyle bit by bit.
Like you, I compared my disease profile to research papers - and the outlook is shite. And then I went looking for answers to questions that the research papers didn't answer. Like - what co-morbidities did their sample have? How old were they at diagnosis (admittedly that question is often included)? What sort of lifestyle did the sample follow? We're they obese lounge lizards who smoked and subsisted on cream cake and wine?
They never report any of that!
It was then I realised that I could not relate the statistical data to me. Medical research by its nature does not orient towards case studies, but each of us is completely unique case study.
I found great solace in the work of Professor Tim Spector and the Zoe project (based in the UK) that is exploring the impact of the microbiome. They simply don't know how powerful, or the role of, it is. While their work centres around heart disease etc, they're starting to look at Tumour based cancers too. I see from an earlier comment that you're seeking some dietary guidance. Have a look at his work, you might find it inspiring.
I worry I'm going to cark it sooner than I wish, but then I realised my lifestyle is healthier than it has ever been, and I try to be grateful for those shocking blood numbers. Good luck at finding a space of positivity.
When you say you have no potential donor's for sct have you had a doctor do a run against various donor registries or are you just thinking of relatives? Even if the former, new donor's are being added all the time so things can change
Hey Merlisa 👋 I saw your post today when looking for any information on ASXL1, in the space of 2 weeks I’ve been told I have intermediate 2 stage MF, JAK2 positive and only today told about the ASXL1 mutation, I’ve been asked to contact my siblings for donor testing as they want to get all my ducks in a row I presume due to the mutation they will look at transplant sooner rather than later 😔 Like you I’m very overwhelmed and scared about my future, I am normally a very growth mindset kind of gal but the prognosis and life limiting timeline they gave me struck the fear of god into me, I am a mum to a beautiful 12 year old boy and the very thought of not being with him terrifies me 😱 I’ve been taking ruxolitonib this is my 14th day and when checking blood counts today my WBC has came down from 28.000 to 18.000 so that’s the positive I’m taking from todays hospital visit, your post actually gave me some hope given the reversal you have seen and I wanted to reach out and tell you that although your post was driven by fear you actually gave me some hope 🙏 Stay positive stay strong and look forward to hearing how you continue to beat the odds 💪 x
ASXL1 is a gene with poor prognosis, directly increasing the MPN prognosis score, and there is no drug to control this gene, so you will be notified to search for a donor. But after all, that is an unpredictable path, and I believe that anti human operations are only done for the sake of survival. As for what will happen in the future, doctors cannot track the rest of your life. They only have data from 5 years after transplantation, but as a patient, your expectations are not just these 5 years. I hope to have a medicine soon that can at least slow down its development process.
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