Post by MPN-MATE Admin » Sun Sep 20, 2020 3:05 pm
Hey guys... 
I have always been interested in Genomic Testing to help prognosis understanding...
This Video, features a Dr Raajit K. Rampal, Memorial Sloan Kettering Cancer Center, New York, USA who was asked via MPN HUB the question:
HOW SHOULD GENOMIC ASSESSMENT IN MF BE PERFORMED?
mpn-mate.com/forum/viewtopi...
Stay safe & well...
Steve
Interesting commentary. I think it should apply more widely to other MPNs. Not yet in clinical practice, but considering the totality of genetics is ultimately key to understanding why MPNs play out is such different ways. Thanks for posting it.
FYI - I am having the IntelliGEN Myeloid Panel run in a couple of weeks. I will post the results. Hopefully all negative other than the JAK2. Also rerunning the JAK2 Quantitative Analysis. We will see what we see.
Hey Hunter... 
Hope all's well in your world...
Yes, I would also like to see more testing for High Risk (HR) mutations, and along w/ 'Allele Burdens' of all known 'Driver Mutations' become commonplace at the outset of one's diagnosis, in order to create the required 'benchmarks' that might make tracking one's MPN progression a tad less toilsome etc...
I had the HR Panel completed some time ago and that was how I learned of my ASXL1+ status, along w/ my reconfirmation of my Driver 'CALR+ Type2 mutation. Having known what my allele burden might have been could have been most useful, although not as sure knowing it is so pertinent any longer...
In Australia, to date, one does not hear much about MPN Patients having results provided for ' Driver Allele' burdens, if anyone who reads these words knows of such tests being performed in Australia. I really would love to hear from you too please...
Be very interested to find out your results too Hunter of course, do keep us Posted buddy...
Best
Steve
Will do when the results come in. Of some related interest, I did have a cytokine panel run. Results not quite what I expected. The only cytokine above norm was IL-10, which is actually an anti-inflammatory cytokine. I had previously been tested for another cytokine and TF Growth Factor beta was mildly elevated. TFN-a was actually rather low. Of interest, nearly every inflammatory cytokine tested was at the top of the "normal" range. The Functional Med doc reviewed it with me, noting the IL-10 could be related to inflammation in the body. Maybe in the brain?? We do not really know, but it is just another piece in the puzzle. I know cytokine testing is not standard medical practice, but given how much inflammation I deal with, I wanted to know.
Thanks for sharing Hunter5582. That’s an interesting field.
« The mechanisms which lead to myelofibrosis, primary or secondary, are still an enigma. It is likely that in bone marrow cytokines secreted by MPN cells, in particular megakaryocytes, could induce activation of fibroblasts and endothelial cells. Moreover, circulating cytokines (not originating from bone marrow) could by themselves influence the bone marrow microenvironment and thereby contribute to the development of myelofibrosis. Hence, circulating cytokines represent an interesting opportunity of simple, accessible, and easily measurable biomarkers for the evaluation of the disease at diagnosis (in addition to usual genetic and clinical markers), but also the determination of prognosis. » ncbi.nlm.nih.gov/pmc/articl...
I really do hope more will come to light about the issue of cytokines and how they play a role in MPNs. I am quite certain this really is an issue for us. Unfortunately there is just enough known yet for it to become common clinical practice to look at this. I am fortunate to have an Integrative Med doc who does look at issues like this. Most docs do not. The panel I did contained 11 of the interleukins and TNF-a. There are many more cytokines than those, but it was at least a starting point to think about. Thanks for including the link to the article.
Hey Manouche...
Thanks for Posting your article Link on areas concerning the 'Inflammatory' markers that may prove of future interest in better understanding some of the processes at work in MPNs...
The "passage' that you cited does actually sum it all up rather neatly and also provides the final result in its statement:
"The mechanisms which lead to myelofibrosis, primary or secondary, are still an enigma..."
One definition of an 'Enigma' : "...enigma means something or someone puzzling, mysterious or inexplicable..."
Or in other words, the article merely provides inconclusive speculations concerning the causes of 'Inflammation'.
Inflammation, in otherwise healthier people is a normal response to the body's healing process, whenever a wound or an infection is caused, our bodies rush resources to those affected areas to resolve and heal us. People w/ MPNs however, suffer from a mutation, that Drives an over abundance, or 'Proliferation' of unwanted 'Inflammation', (Cytokine storms etc), and can in certain instances create more adverse outcomes.
That is why, in my own humble view, implementing an 'Anti-Inflammatory' dietary regime, coupled w/ a meaningful exercise can truly help us MPNers sustain our longevity well into our MPN journeys.
Nevertheless Manouche, it is a very interesting article all the same, even though their findings do not appear, (on the face of their work), to truly support their overall hypothesis, in my view...
Stay safe & well my friend
Steve
Hi Steve, I agree with you regarding diet/exercise as important factors to our longevity.
An « enigma » and a « mystery » are two different entities. Unlike the latter, an enigma can be solved. I’m quite convinced this « inflammation » enigma will be solved in the next few years 🤞
Keep moving and eating well!
Hey Manouche...
Hopefully, someday the mystery will be solved, and we will ALL have a true cure for these MPN mutation conditions...
Best wishes
Steve
Hunter - I just googled the IntelliGEN test - didn’t get a great sense of what data you’d receive. Presumably tells you which in the laundry list of mutated genes you have? Is there some algo that takes the gene mutant positives to indicate probabilistically what one is destined for, ie, MF, AML, etc? Or is just a dot in a box like they show on the webpage?
There is no test that can predict precisely how your MPN will manifest. Using the most common driver mutation as an example, JAK2v617f can cause ET, PV or MF. It can begin as one disease and progress into another. It is not understood precisely why this is so. There are theories, but no clear answers. We do know that mutant allele burden plays a role. The degree to which the JAK2 mutation is heterozygous or homozygous can also play a role. We also know that the non-driver mutations play a role in severity, presentation and and progression of the MPN. I am not looking for precision diagnostics in having the myeloid panel done. I am looking to get a better sense of what the status of my MPN is and what my risk profile looks like based on hard data. I already know I am at increased risk for leukemic progression since I also have the NF1 mutation. As I consider my treatment options, I want to have a more accurate picture of all of the factors that are in play. What I am doing is not in common clinical practice, though I think it should be. Enough is known at this point to understand that the non-driver mutations do play a significant role. I believe more information can lead to more informed decisions. It is possible that my PV is progressing, thought that is not certain. I want to make the best decisions possible based on the best information possible. Many docs would not bother with what I am choosing to do; however, I am responsible for my own treatment. I will base my decisions on what we learn.
Love this response Hunter (as usual). Agreed we need to be proactive to get the best treatment possible. Look forward to your insights on the usefulness of this test - perhaps it’s something many of us here should consider....if insurance will cooperate...
MF and bone marrow transplant
MF, considering interferon treatment
Molecular remission of MF which is being treated with PEG 
