In this study I just posed on there is a brief reference to using MRI for bone marrow.
ashpublications.org/blood/a...
"...bone marrow MRI results (in PV pts) will be presented in the final report."
An example here MRI found abnormalities in leukemia pts:
ncbi.nlm.nih.gov/pmc/articl...
I've read some about it but this is the 1st I've seen of its use for real. I know it's more limited than a biopsy but if this study is using it there must be things we care about via this method.
Marrow MRI would be a good addition to the tools used to assess MPNs. It would miss some data available from a BMB, but avoid an invasive uncomfortable procedure. It is good to have more options.
High-resolution MRI will certainly be able to see fibrosis development in bone marrow. As those linked papers indicate, however, MRI is more likely to “accidentally” reveal the presence of abnormal bone marrow rather than become a substitute for bone marrow biopsy. The BMB is capable of revealing so much more information at the molecular level that it will (almost?) always be chosen. Periodic MRI scans could potentially be an interesting way of monitoring the progression (or not) of fibrosis. Since the BMB takes just a small sample of the marrow, I don’t know if that is truly representative of the extent of fibrosis that a patient has. In other words, I don’t know if fibrosis is pretty homogeneous in distribution or if it is heterogeneous. If it is heterogeneous, then MRI could be helpful.
Good point on the local variations, it is a known issue in BMB.
MRI could be a good way to have relative values over time as you say esp if there is a BMB reference with a same-time MRI. Any changes of interest could indicate getting another BMB while no changes in MRI or other conditions could put off the next BMB.
Brings up the question would MRI of the shoulder area for example provide any marrow info? Or maybe it's only useful if done near where BMBs are usually done.
My PV was found as a consequence of an MRI. I was getting my Prostate checked out and it showed marks on my pelvic bone marrow. That lead to other checks and here I am.
Why do you ask about an MRI of the shoulder? Indeed, it seems that it could be informative, if we assume that fibrosis is heterogeneous. This raises a question I have wondered about: is bone pain associated with fibrosis at all? My bone pain is certainly not equally noticeable in all my large bones.
You're right shoulder is sort of arbitrary, I got one there for my Parsonage Turner Syndrome neuro condition that was from the flu vax, so a good example of a place where an MPN finding could have been quite incidental. I also got for the brain and spine, but these areas likely would show nothing of interest in the marrow.
Typical concepts of bone pain in MPN is the excess blood cells create pressure in the bones, but it seems, as always, there are other complex issues at play. I've had some minor bone pain recently but bloods are ok other than in-range but high PLT.
Thanks for the insight on bone pain origin. I hadn’t thought of that reason.
If this is the main source then having CHR should keep a lid on it. But there are likely exceptions and maybe how one gets to CHR makes a diff. For example IFN gets to the deep source while HU acts farther downstream, does IFN reduce bone pain better than HU? Could be...
HU inhibits ribonucleotide reductase (aka ribonucleoside diphosphate reductase), thus diminishing the deoxynucleotides needed for DNA synthesis. I suppose this hinders production of more HSCs and will then keep our platelet levels down as well as diminish extramedullary hematopoiesis (thus diminishing spleen size). Unfortunately, it also inhibits DNA production for many things that are good for us. Interferons, on the other hand, are anti-inflammatory proteins that counteract some proinflammatory cytokines that have been ramped up with our MPNs. I haven’t looked into exactly which one has been modified by pegylation to serve as a drug for MPN.
My thought is the deeper the effect the more useful it should be. IFN is nominally the deepest of the three (HU,Rux,IFN) This is very simplified thinking which is limited but my fav way to look at things.
For pegylation, all current IFNs are that. Non-pegylated is not in standard clinical use anymore since the frequent dosing and drug level variations were hard to tolerate. The pegylated include IFN alphas Pegasys, Besremi and PLEGRIDY (IFN-beta for MS)
Well, there are many more interferons than alpha and beta, although I’m sure there were reasons to choose those. Pegylation is a logical way to modify a protein to reduce its degradation (and therefore need to get another dose so soon). You’re right that using something like a DNA synthesis inhibitor, such as HU, is a pretty crude way to approach the problem. However, I would argue that using JAK2 inhibitors are a relatively sophisticated approach although still too broad in that they affect more than we would like. Choosing to try interferons was rather obvious to combat the cytokine-inducing MPNs and, fortunately, they seem to work for many cases. But they still are not as selective for our disease as one could hope. More sophisticated approaches, such as targeting histone H3K4 demethylase LSD1 (lysine-specific demethylase), that is a key regulator of hematopoietic differentiation, I hope will be successful; the initial work on bomedemstat certainly looks promising.
IFN gamma is a third well known one, but I'm not familiar with its use in therapy. I think its a stronger and scarier form when in excess.
I have a bias lately to agree on the Jak-i's since I'm on Rux now. The latest reports are compelling for it, and I'm actually seeking its off target effects to reduce autoimmune troubles. IFN+Rux is esp compelling in recent reports.
From what I've read, a key action of IFN was unexpected, wherein it preferentially activates the clone and eliminates it via exhaustion. This is weird but effective, possibly from IFN's ability to also increase cytokine activity as well as reduce it. It was once expected that Rux would counteract this increase and reduce the benefit of IFN. Much of science is throw our best ideas in the pot and see what works. AI should help greatly to select what to cook.
Bom seems to be looking good, but not big magic. It is looking good for PLT reduction however. One member had to go off it in trial. A recent report suggests it might also work well as adjunct therapy.
Likely the ultimate fix is what's already in progress for CALR and many other conditions, immunotherapy to target the clones directly. This has lots of reports just the last year or so. CALR has a shot of being curable this way. Jak2 is a bigger challenge but there is early progress there too.
Actually, there are 15-20 different interferons. They have a few different basic mechanisms by which they mess with the immune system.
Regarding bomedemstat, it has shown promise but is not going to be a magical “cure”. What I was referring to is the ever more sophisticated choice of targets. I am sure a better molecule exists that could bind to the same target as bomedemstat. However, as the molecular biology underlying the pathology is illuminated, the better the chance of finding more specific targets for drug development. One of our problems, however, is that there are far fewer of us suffering from MPNs than other diseases, so there are fewer research funds available for revealing this molecular biology and especially for the expense necessary for drug development.
Bone marrow biopsy pain
ET and bone marrow biopsy 
Bone marrow result - cryptic
Bone marrow biopsy results.
Bone marrow biopsy first time 
