St, Jak2, and now Asxl1...

[Mortysdad]

Hi gang,So my quick journey so far, my elevated platelets over the past 2 years, up to 950, led to deeper bloodwork last October discovering Mpn possibilities with the Jak 2 mutation. Fatigue and itching most notably. Met with my Hemo, the great doctor Palmer at Mayo who set up a bone marrow biopsy. It confirmed, and I started Pegasys. 3 months in, my platelets were still in the low 8's and we did a consult. Dr said that she wanted them to come down quicker and would normally add Hydroxy at this point, but instead increased my dosage of Peg. Said that an Aslx1 mutation at 26% was also discovered in my BMB, and that this mutation is always found in Lukemia patients. Said there is some concern about adding the H because of this. Said they have no treatment for this and will continue to address my platelet issue. Also said it can be aggressive. When I Google Asxl1, which I was told not to, I find it comes with a "poor prognosis" label, but very little else. I was just getting comfort from my group of peers out there that have conquered ET/ Jak2 for years, and now this...looking for some positivity from any in the same boat out there?

Blessings!

[hunter5582]

It sounds like you have a great doc who is right on track with your treatment protocol. The rationale you explain makes very good sense. You are fortunately to have a hematologist on your case who obviously understands MPNs.

I would agree with not random Googling ASXL1. It will take you down rabbit holes that are not helpful and in many cases not relevant. The short version is that the ASXL1 mutation is a non-driver mutation for MPNs. Having this mutation along with the JAK2 mutation increases the risk of progression. That does not mean that it is likely to happen, just that there is a higher probability than if you did not have the additional mutation.

Like you, I have two mutations in my profile. In my case it is AK2 and NF1. Together the two mutations increase my risk of progression. They also increase my risk of other neoplasms. I do not, however, worry about it. I do something about it instead. I opted for treatment with the Interferons, Pegasys/Besremi, to reduce my risk of progression. In 18 months on low doses, my JAK2 allele burden has reduced from 38% to 9%. I am in a complete hematologic response. It appears I am, hopefully, headed towards a deep molecular remission. That is not all I have done. I also reduced exposure to environmental toxins and contaminants in the food stream. I exercise and work to keep the weight off. I stick. mostly, to a Mediterranean diet. I work with my Integrative Medicine doc to control systemic inflammation.

I am doing what I can to reduce my risk of progression. I feel better than ever. Much better than I did before starting on the IFNs and making the other changes.

Suggest not sweating the things you cannot change. Change the things you can that will improve your odds and the quality of your life. If you really want to learn more, you can look into the research on the MPN non-driver mutations like ASXL1. That is more focussed and meaningful than looking at all manifestations of ASXL1.

We can't change our genes, yet, but we can change how we manage our conditions. We can improve our odds, extend our lives, and live better by the choices we make.

[Mortysdad in reply to hunter5582]

Why thank you Hunter! That is exactly the boost I needed today. I am usually a living example of the Serenity Prayer...just need a reminder sometimes. Thank you and absolutely agree with you on all points. Stay well and keep encouraging others, it's huge!

[mfh7]

I also have the Asxl1 mutation (10%) with jak2 and went down that same research rabbit hole. I came to the conclusion that there is no definitive answer but some indication that the Asxl1 may increase odds of progression. Basically what Hunter said exactly in terms of his assessment and recommendations. Don’t sweat what you can’t control and do what you can to live your best and healthiest life. Also there are many worse things you could have than this mpn so count your blessings. Best of luck!

[Mortysdad in reply to mfh7]

Thank you for the confirmation. How long have you known about your asxl1 mutation? As I count my blessings, I quickly run out of fingers. Appreciate you all here!

[mfh7 in reply to Mortysdad]

I found out about Asxl1 after a bone marrow biopsy that I had to establish a baseline of my allele burden for jak2 prior to starting Besremi about 14 months ago. Have not had one since then because it is expensive and insurance doesn’t cover a lot of it. I will be curious to eventually see if Besremi has lowered my Jak allele burden at some point when he get another bmb. Besremi has helped my numbers a lot but still need phlebotomy app every 2 1/2 months. At max dose of 500 mcgs and hoping it kicks in for hct control soon.

[lakeview65]

I too have Askl1 32% and jak2 at 9%. I was diagnosed July of 2021 and I have seen 2 hematologists and 1 MPN specialist , no one has an answer and I ask. Poor Prognosis and an increased chance of AML, but only slightly. I was told on more than one occasion that this was my driver mutation. I have been on Hydroxyurea for 18 months now and no one has ever told me it wasn’t a good option for me. My BMB results did say Pegasys would likely not work for me.

My platelets are just under 500 taking 9 pills a week and I do not want to increase the dosage unless they go higher. I wish I had more info, I understand how you feel. I try not to think about it too often. I cannot change it but I will ask my local Dr. what he thinks about being on Hydroxy and ASKL1.

You are not alone.

[Mortysdad in reply to lakeview65]

Thank you Lakeview65. Your right, not alone helps one cope just knowing there are others walking this road. I do know too that even as we identify by the big label mutations we have, a BMB reveals so many other characteristics that get added into the mix so our pathways of treatment don't always look the same. Still, we are all in the same camp, so very grateful for my fellow campers! Stay well....