JAK2 mutation

And for MPN, this is definitely We have the kind of Damoshek era and PBSG broad management diagnostic criteria.

Then there was a description of the JAK2 V617F mutations simultaneously by several groups around the world.

And very notably Radek Skoda was awarded the Ernest Buehler prize recently for that.

And then shortly after that, NPL mutations and then Kevlar mutations, and then After that came targeted therapies, but they're not really addressing the mutation as such.

It's that finding first.

to me that has always spoke to the idea that there is an anti-clonal effect of this drug you're reducing the disease burden the mutation is a surrogate for that burden and with that reduction is the idea of tying it into a progression for your event-free survival and a lot of that data comes from polycythemia, specifically with ROPEG and the PROUD-PV study where Heinz Gislinger and folks have published very nicely that there is a relationship between a 50% reduction in JAK2V617F and event-free survival, so clotting and bleeding and progression of disease.

And that makes sense because as a validating study, MAGIC-PV study that Claire Harrison ran with Ruxolinib in the hydroxyurea failure patients with PV also demonstrated a 50% reduction in BAF was associated with an event-free survival.

So I think we're beginning to embrace, and maybe not the FDA, but we are beginning to embrace that reduction in these driver mutations, and it's not a perfect science, but is associated with better outcome.

Because there's a ton of data that has demonstrated that in ET and PV, a higher JAK2V617FVAP is associated with higher venous thrombosis rate, progression of disease, and worse survival.

So

it's all there.

I think up until a very short time ago, you still saw patients in the clinic.

You've founded a company to really focus on targeting the JAK2V617F.

mutation so pretty busy number of roles so first of all how do you manage to do all the things that you do and secondly you know why is it important for you to to have these roles and and particularly why is it important you know after 20 years you're still in academia you're still mentoring people you know you're still doing science what is it about those things that keep you here as a physician scientist

That's a lot of really good questions.