I preface this post with stating that this is merely my personal perspective/opinion as a young (age 30) potentially triple-negative ET individual based on my own research having been in the diagnosis process for a couple months now.
I've seen triple-negative ET described in this forum many times as the "most benign form" of ET. However, to me, this seems somewhat misleading in that it appears to be biased toward the largest portion of the ET population (patients diagnosed at older age) because the "most benign" designation appears to be strictly based on thrombotic risk (the short-term threat) rather than risk of disease progression (the long-term threat).
Most, if not all, studies I have read comparing the long-term progression risk of ET have determined that triple-negative ET, particularly after 20 years, has a significantly higher risk of disease progression to AML compared to ET with JAK2, CALR, or MPL. Additionally, after progression, triple-negative MF/AML have a significantly poorer prognosis compared to those with driver mutations. This is believed to be primarily due to the higher rate of "non-driver mutations". Triple-negatives have a much higher rate of non-driver mutations than those with JAK2, CALR, and MPL. My understanding is that the driver mutations are more influential in causing the disease phenotype itself (hematopoesis), and the non-driver mutations are more influential in disease progression (and are involved in many other cancers).
So, for the majority of the ET population (older patients diagnosed when they are already somewhat close to a "normal lifespan"), yes, triple-negative ET may indeed be more benign since the risk of thrombosis is lower, meaning they are perhaps more likely to die of something other than their ET since they would expect to live approximately (or less) than 20 years from diagnosis anyway even if they did not have an MPN. However, for younger patients who still have 30, 40, 50 more years to live to a "normal lifespan", it seems triple-negative ET is actually greater overall risk in the long-term to living a normal lifespan compared to those with a driver mutation due to the increased risk of progression.
Of course, everyone's disease is different, and the prognosis of an individual is very different than looking at large groups of people, but it seems to me that this is what the evidence suggests as a general trend.
Would appreciate anyone's thoughts on this.