ET calr and inflammation

[Bohus]

Hello friends! I was reading a couple of posts in the forum regarding the effect ET jak+ has on cytokines in the body. Since I have the calr-mutation I was wondering whether my cytokine levels is affected as well? Does anyone know about this?

[Grendall]

Hi Bohus

I too am currently ET with the Calr mutation.

For me yes, very much so it does affect the cykotines, i appear to have all sorts going on in my body and a very low immune system. Started on Interferon injections 2 weeks ago, yesterday being my second therefore a bit early to notice any changes yet.

I have just had a bout of ‘tooth abscess and then shingles’ so had a rough few weeks, for me it does appear to be battering my immune system at the minute…

[socrates_8]

Hey there Bohus & Grendall...

My name is Steve, (from Sydney, Oz). I am 63yo, Post ET / MF CALR+ Type2, w/ HRM ASXL1+ & also Von Willebrands Syndrome (VWS- acquired?).

Your Post concerning "CALR" 'Driver mutations, piqued my curiosity also... Thanks for sharing your thoughts...

I was initially diagnosed by accident in 2016, & through researching my MPN, (some time ago now), I came to learn a tad more about the over 50+ different types of 'CALR' mutations, (the greater majority of CALR is found in either Type1 or Type2 mutations, circa 80+%). However, & depending upon who you might ask, (or whose research you might follow), generally speaking – Type2 CALR, usually indicates a higher Platelet regime & therefore raises concerns regarding Thrombotic events. In contrast, CALR Type1, is considered more benign, both w/ Platelet levels & concerns of thrombotic events.

NB**( All of the claims above were gleaned from a broad range of peer-reviewed articles, which I am NOT citing here in this POST - However, I am willing to dig them up if it's truly required)...

However, this is just my own research efforts via accessing Medical journals & other "peer-reviewed" scientific articles... I confess to not being any sort of medical or research expert, & just another MPN patient who discovered that most GPs & Haematologists, knew/know very little about MPN blood cancers, & that fact alone I found most disturbing... Don't you?

There is of course contravening research, that might suggest the converse of CALR Types 1 & 2 might also be true. However, in the greater scheme of things, & through ALL the research I have appraised myself of thus far... They all suggest that CALR itself, usually indicates a greatly lessened likelihood of "thrombosis"...

My gene mutations indicate that I am CALR Type2, & thus far I have suffered from Two (2) & possibly Three (3) TIAs, (minor brain strokes).

In my own experiences, it seems to me that whenever my Platelets escalate above 1M benchmark, other symptoms also tend to appear, ( I now call these my Red Flags):

* Tinnitus

* Global headache

* Vision impairment, (monocular)

* Facial twitch especially on my lips

* Mental fugue (Brain fog)

When I was diagnosed, I was back studying at Uni' & due to that fact, I still had such wonderful access to university libraries ...

Hence, & so to return to your original question:

"Cytokine Storms" (in my view), are in fact a problem related to bodily "Inflammation"

It's also imperative to understand that "Inflammation" in the normal sense of how it appears in our bodies, is generally a very good thing. Inflammation is caused in the very 'Normal' process of our bodies endeavouring to heal themselves...

However, our MPN "Driver" mutations, be it: JAK2, CALR, MPL, or one of the other even more rare "Drivers', cause our bodies to proliferate our incorrectly cloned, & mutated cells, which in turn gives us our MPN illnesses etc...

Therefore, anything that helps to reduce our bodily inflammation, might also help us manage our MPNs a tad better(?)

Such is my theory that I like to work w/...

My response, is to try to maintain my "Anti-inflammatory" diet, coupled w/ my cycling exercise, & I am still here... :-))

Anyways, thanks for sharing your Post...

Best wishes guys, stay happy, safe & well...

Steve

[hunter5582]

The short answer to your question is that the CALR mutation upregulates the JAK-STAT pathway in a manner similar to JAK2 mutations. This includes inflammatory cytokine production.

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

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

frontiersin.org/articles/10...