The short answer to your question is that VAF does matter. It is linked to progression and symptom burden; however, there is not a 1:1 correlation. The reality is far more complex than that.

The recent article by Moliterno et al does a nice job summarizing the issue.
https://ashpublications.org/blood/article/141/1...

JAK2V617F allele burden in polycythemia vera: burden of proof

https://ashpublications.org/blood/article/141/16/1934/494354/JAK2V617F-allele-burden-in-polycythemia-vera

Hi Ren,

That is a very important aspect we all want answers for.
I am a bit unwell so I will leave a longer answer for another time, but in short it seems this is a complex matter, based on the mutation you have, whether you have only one mutation or several and also whether your illness is hereditary. As a rule of thumb, if you are young and your VAF is >50%, then there is a possibility you have hereditary MPN, so that should be investigated first. Many cases of MPNs were missed in the past, so one could not be aware this ran in the family.

The two studies below look at JAK2 mutations and CALR mutations and how VAF can influence prognosis:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC86...
https://ashpublications.org/blood/article/140/S...

Given the small rather local samples, I would take the results with a pinch of salt. Also, due to small sample size and the fact that some risk factors tend to overlap, some of the risk estimated are, most likely, inflated and sample dependent.

This is a very individual illness and probably this is adding even more to the uncertainty that MPNs already bring to our lives.

The way I handle this is being aware of the fact that doom & gloom studies have so many methodological issues that a crystal ball can be more accurate at times. My way of dealing with uncertainty.

Many hugs of support,
Tatiana

JAK2V617F variant allele frequency >50% identifies patients with polycythemia vera at high risk for venous thrombosis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665926/