ASXL1 and TET2 Gene Mutuations

[majorindy]

Anyone been diagnosed with these two gene mutations. If yes, how long ago and your present status. My present diagnosis is MDS Low Risk but everything I read about these two mutations point to a much shorter survival time. Seems puzzling to me that they say get a blood test every three months when it appears things could change quickly.

[Data]

Major.
I had an extensive gene mutation study done in Jan 2016. I had both ASXL1 and TET2 among many others. I have attached the results.
I was listed as high risk (not very high) mainly because I had monosomy 7. I had a transplant in April 2016. I have never recovered energy wise or blood count wise.

Gene Mutations.pdf

Cheers

Data

[Barb M]

I received a confirmed diagnosis in Dec of 2013 thru a bone marrow biopsy and gene sequencing. The AXL1 gene was found.

Was told the same thing about poor prognosis. Still here.

[Hopeful]

Originally Posted by majorindy

Anyone been diagnosed with these two gene mutations. If yes, how long ago and your present status. My present diagnosis is MDS Low Risk but everything I read about these two mutations point to a much shorter survival time. Seems puzzling to me that they say get a blood test every three months when it appears things could change quickly.

Hi Marjoindy,

The field of genomics is so new and rapidly changing that I don't think conclusions can be made about any specific mutation yet. It is my understanding that having a mutation doesn't mean that you will necessarily get a specific disease. It just means that you are statistically more likely to, should that gene become activated. Barb is good case in point. I am watching one of the AAMDSIF on-line courses and the treatment of care for someone in the low risk group, even with gene mutations, is to monitor counts every 1-6 months. If you would like things monitored more frequently for your own piece of mind, I am sure your doctors would honor your request. It seems like a very reasonable request to me!

Good luck, and I hope things stay stable!

[Bossywife]

My husband is also low risk (RAEB 1) but he gets tested every month because he plays hockey. If his platelets go below 40, he has to quit playing.

We just had the Myeloid Gene Panel done and are awaiting results.

[Sue&Dave]

My husband also has the ASXL1 mutation along with CBL. We too were told that the ASXL1 is associated with a poorer prognosis, but no one really told us why - is it more resistant to treatment? Less favorable outcome after SCT? That said - he has had a remarkable response to Vidaza (starts his 9th round next month), so much so that his counts are almost all normal now. I like Barb's response - 4 years later and she's still kicking

[Data]

This is from the NIH.

ASXL1 gene provides instructions for making a protein that is involved in a process known as chromatin remodeling. Chromatin is the complex of DNA and proteins that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. When DNA is tightly packed, gene activity (expression) is lower than when DNA is loosely packed.

Through its role in chromatin remodeling, the ASXL1 protein regulates the expression of many genes, including a group of genes known as HOX genes, which play important roles in development before birth. The ASXL1 protein can turn on (activate) or turn off (repress) HOX genes depending on when they are needed.

The ASXL1 protein may have an additional role in gene regulation by signaling to molecules to add a methyl group (a process called methylation) to an area near a gene called the promoter region, which controls gene activity. When a promoter region is methylated, gene activity is repressed, and when a promoter region is not methylated, the gene is active.