PIM1 Mutation in addition to JAK2?

[LIGEBA]

Any of you who have a JAK2 mutation, have you later been diagnosed with a PIM1 mutation as well? If so, can you share what you know about it? Thank you.

[hunter5582]

Pim1 is involved in a variety of cancers. You may find these two articles to be a good starting point to understand this particular issue.

Pim kinases (Provirus Integration site for Moloney leukemia virus) are a family of serine/threonine protein kinases with roles in cellular development, immunoregulation, and oncogenesis. molecular-cancer.biomedcent...

JAK/STAT Pim-1 plays a role in BCR-ABL-mediated cellular transformation. BCR-ABL activates leukemia cells via signal transducer and activator of transcription (STAT5) and upregulates the expression of Pim-1 ncbi.nlm.nih.gov/pmc/articl....

This is not mutation many of us know about. Please do let us know what you learn. Everyone can benefit from your experience and knowledge.

[LIGEBA in reply to hunter5582]

Thanks. I did see these articles and can't seem to make sense of them. I reached out to my MPN dr. to see if I could get a sense of if this was something to be greatly concerned about, or if it was something on the normal side given my issues. The response from the nurse was I needed to wait the 2.5 months until my next appointment. I can be super patient with most things, but something like this isn't 1 of them. I will report back as soon as I find out anything.

[hunter5582 in reply to LIGEBA]

These articles are a bit esoteric. The short version is that there seems to be some sort of association with the BCR-ACL mutation (AKA Philadelphia Chromosome) that causes CMML. With MPNs, we experience the Philadelphia Negative MPNs. There may be some sort of connection to your case of MPN, but I do not know what it is.

It is rather insensitive of the nurse to tell you to wait 2.5 months when you have a legitimate concern about this finding. Suggest reaching out to the hematologist directly via email or patient portal to let the doc know you are concerned. If that fails, perhaps you can seek an opinion elsewhere.

Please do let us know how you get on and what you learn.

[EPguy]

There is an interesting connection to Jak2 and PIM1.

"Combination of various PIM inhibitors with a JAK2 inhibitor (ie Jakafi) results in significant synergistic growth inhibition of multiple MPN cancer cell lines and induction of apoptosis." Multiple lines suggests not just Jak2.

ncbi.nlm.nih.gov/pmc/articl...

The target to inhibit is "MYC".

According to :

thelancet.com/journals/ebio...

"compound KSI-3716" can target MYC. But it's pre-clinical.

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Hunter's link also has this:

PIM is "Often up-regulated following JAK/STAT and tyrosine kinase receptor signaling"

So your MPN (JakSTAT influenced) and PIM have at least some connection.

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The 1st link here brings up a question for all of us, is this a potential combo therapy we should know more about? For you it could be a specific opportunity if your Dr considers treating your PIM1 condition if/when KSI-3716 or its like becomes available: you could be a natural for this combo Jak+ MYC inhibitor.