Anyone have any of these three mutations tested for?
--
This study evaluated the impact of co-occurring mutations and clinical characteristics on prognosis in 85 patients with WHO-defined polycythemia vera (PV). Overall, 84 patients harbored a JAK2 V617F mutation. An additional mutation was identified in 78% of patients, with mutations in ASXL1, TET2, and DNMT3A being most frequently co-mutated. Patients harboring more mutations had shorter overall survival, and patients with co-mutations in ASXL1 (8.2%) had significantly lower 5-year overall survival rates as compared with non-mutated patients (43% vs 74%). In patients without ASXL1 mutations, age and prior history of thrombosis before PV diagnosis were associated with an inferior overall survival.
The presence of ASXL1 mutations in PV appears to be associated with an inferior overall survival. For patients without ASXL1 mutations, age and prior history of vascular complications are associated with overall survival. These three risk factors appear to be valuable for risk stratification of patients with PV.
This is very difficult to Interpret even as someone who has a health background. Basically are they saying if you have extra mutations your life expectancy could be reduced despite treatment?
I havent had any additional testing though who knows what was originally tested....I asked my hematologist about this though. I also had my dna sequenced a couple of years ago through 23andMe and was attempting to look at the raw chromosomal data....but hard to decipher it all.
The genetics that underlie MPNs are quite complex. The study you are citing replicates previous studies showing the same finding. Here is a another study, along with an excerpt addressing the ASXL1 mutation.
The ASXL1 gene is one of the most frequently mutated genes in malignant myeloid diseases. The ASXL1 protein belongs to protein complexes involved in the epigenetic regulation of gene expression. ASXL1 mutations are found in myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). They are generally associated with signs of aggressiveness and poor clinical outcome. Because of this, a systematic determination of ASXL1 mutational status in myeloid malignancies should help in prognosis assessment.
There are other gene mutations associated with higher risk in MPNs.
PV risk increase – ASXL1, SRSF2, IDH2, TET2
ET risk increase– SH2B3, IDH2, SF3B1, U2AF1, EZH2, TP53
Tefferi et al, Blood Advances, Nov 2016
AML Transformation: DNMT3A, IDH1/2, SRSF2
Additional non-driver mutations found in ET/PV Cases – MF/AML Transformation:
So what does this all mean? There is awareness of the role of the driver mutations (JAK2, CALR, MPL) in causing the MPN and the potential role that the mutant allele burden has in the progression of the illness. What is emerging is the role of the non-driver mutations play in the outcome. Note that these non-driver mutations play a role in many cancers/neoplasms. They can exacerbate the symptoms of the MPN and contribute to disease progression.
I became more aware of this when the docs checked the brain tumor I had removed for many of these same gene mutations. I am positive for the NF1 mutation (I have Neurofibromatosis type 1 and PV), but the brain tumor (grade1 pilocytic astrocytoma) was negative for all 27 cancer genes they checked for. This was really good news as the NF1 mutation puts me at higher risk for transformation into a malignancy. The NF1 also puts me at higher risk vis-à-vis the outcome of the PV. Frankly, I do not worry about it as it is something over which I have no control.
As I understand it, most docs do not check for the non-driver mutations unless there is a reason to do so. In the absence of a particularly aggressive MPN, apparently these mutations are not routinely screened at this point. Perhaps at some point this will become part of the protocol, but it is not there now. While some of us would rather not know, which I understand, I think it could be helpful in making treatment decisions. Higher risk would indicate a need for potentially more aggressive treatment in my mind.
Hopefully continued research will shed more light on this issue and benefit us all.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
