Allele Burden and MPNs Explained by Prof. Lucia Masarova

[Manouche]

At the 4th MPN Spring Symposium in Barcelona, Prof. Lucia Masarova, Assistant Professor at The University of Texas MD Anderson Cancer Center, discussed the concept of allele burden and its role in managing Myeloproliferative Neoplasms (MPNs).

gmpnsf.org/post/allele-burd...

[ainslie]

this a good summary, ie she says we hope we know what it means ie AB reduction but we don’t know for sure yet. Note she also says if it goes up don’t panic the patient may be doing perfectly well.

[RoundTheWorld in reply to ainslie]

Yes - sounds like its probably a good thing to reduce AB but it may take years to have clarity based on all our experiences.

I asked my haematologist if I would repeat AB test when I reach a year from diagnosis. She said they may hold off because in some cases people see a rise before a fall; it may be more encouraging to test later (I agree I’d rather feel encouraged than not, although I'm also interested and extra data might be good for research purposes).

What she said fits with something I think the MPN specialist that I met said, but I didn’t pick up on. I think he said mutant cells proliferate more when treatment is started but later wild type cells start to overtake, causing the drop in AB.

I wonder if:

- a suddenly larger volume of mutant cells are easier for our immune system (primed by interferon) to detect and destroy?

- if there is a slowdown in the mutant cell cloning process,

- if treatment causes mutant cells to clone less accurately so resulting new cells fail?

- Or maybe what Dr Beth Psaila talked about in the post Ash summary about perhaps needing to destroy dormant cells as well as active cells plays a part. Maybe our treatments are starting to help that to happen?

[EPguy in reply to RoundTheWorld]

One way IFN depletes the clone is (very roughly) by forcing activity among the mutant cells (un dormanting them) and thus exhausting the clone. This is in some posts a few years ago. So it could be an increase in the clone as all this replication goes on and that may be your Dr's thinking.

But in reality over 6 month periods the median mutation went down rapidly in the Bes trials as seen in this plot. So maybe the exhaustion starts very quickly and overcomes the increase. The one year your Dr refers should show a decline if it's going to happen as we often see here while there are plenty of exceptions. These are medians and most pts will have at least a somewhat different result.

One loose predictor of mutant reduction can be blood count response. Most studies have found a relation between these .

Rux does it differently and I believe was not designed to do it at all, even as it is now known to do.

ropeg

[hsdale3]

Hi Manouche,

Sorry for going off topic however, I had read a post by another member who cited you regarding a new MPN drug that is coming out (was/is currently in trials, I believe). What is the name of the drug, and who is the manufacturer?

Thank you for your help.

Howard

[Manouche in reply to hsdale3]

Hi Howard,

I suppose this is this one: healthunlocked.com/redirect...

[hsdale3 in reply to Manouche]

Manouche, that looks like it. Thank you!

[EPguy in reply to hsdale3]

There are actually three new Jaki's two of which are in phase 1 trials. Manouche has found and discussed these reports and I've then posted in a few places some more details on the three.

[hsdale3 in reply to EPguy]

Can you point me to the posts, or better yet sources of said reports? Thanks

[EPguy in reply to hsdale3]

My posts are sort of scattered on this, there is a lot of info and connected studies in them. I've been wanting to make a fresh post with all of it in one place.

[hsdale3 in reply to EPguy]

Thanks in advance for compiling everything, I really appreciate it. Thanks, again. Howard