Genetic tests

[artydutch]

What can genetic testing find, beyond mutations? I believe they are looking at the megakaryocytes but not totally sure if I heard correctly. What information can the test give? Anyone?

[EPguy]

Megakaryocytes are found in your bone marrow biopsy (BMB). This is a physical shape of features in your marrow. This also looks for cellularity and fibrosis and others, also relating to the physical shape and appearance of your marrow. This is "histology" and they use a microscope to see these. These BMB results help to know which MPN you have, ET, PV, or MF and can help with the prognosis. But I see your prior posts that you already have a Dx.

The mutations are genetic features relating to DNA, so they are not normally seen physically. Rather their chemical make up is checked for which amino acids are in them. Having the wrong ones or missing ones in a gene is usually how they find mutations. They use hi tech genetic methods to look here. These also help with diagnosis and prognosis. The PCR Covid test is also in this genetic category.

They can check your marrow for both histology and mutations.

[artydutch in reply to EPguy]

Thank you for your explanation. I cannot claim to understand all but like to be aware of what is going on in my body. The first genetic test found JAK2 and DNMT3. This latest genetic test I believe is looking more at the abnormality of megakariocytes. They were described as abnormal and clonal in the biopsy report.

[Meatloaf9 in reply to artydutch]

Hi, I had the same results when I was first diagnosed 4 years ago - Jak2+ and DNMT3A. If you find out the significance of the DNMT3A mutation please let us know. My mpn specialist says that the jury is still out on the significance of this mutation. Best to you.

[artydutch in reply to Meatloaf9]

I will do. I believe they do not attach huge significance to Dnmt3 . If I find out any more I will share the info.

[EPguy in reply to artydutch]

We always learn together here. There is in fact a type of mutation unique to megakaryocytes that are not the "regular" ones we are familiar. It seems they are looking for these in your BMB results.

"Abnormal" likely means they have irregular shape and appearance, "Clonal" megakaryocytes means there are mutations in them.

This report is likely related to the Clonal part of your results. I think these are very up-to-date procedures your Dr is doing:

<<These findings show that genomic abnormalities are present in megakaryocytes in MPNs and that these appear to be associated with progression to bone marrow fibrosis.>>

pubmed.ncbi.nlm.nih.gov/285...

--

For DMN3TA there is a post with some info:

<<-Note that TET2 and DNMT3A are not in the high risk category with MF. But high risk ASXL1 is most common non-Jak2 in MF (22%). >>

healthunlocked.com/mpnvoice...

[artydutch in reply to EPguy]

Hi I looked up my histology and the following was in the letter re trephin biopsy, aspirate was dry tap. Fibrosis score 1-2.

“This shows cellular marrow, but with evidence of dyserythropoiesis with an expanded granulopoiesis and increased megakaryocyte numbers. The megakaryocytes have abnormal and proliferative morphology with some clustering”

I have been scored intermediate, so far 1 but this test will inform this diagnosis more, I believe. So far the agreement is to watch and wait. Spleen ok, liver inflamed. I think if I become intermediate 2 by the dipss plus score then perhaps treatment may be considered. I may hear something tomorrow. Thanks for links to articles, I find these useful.

[EPguy in reply to artydutch]

I've posted on cellularity. "Cellular" is normal, all marrow has some, so it could be shorthand for hypercellular. Some level of Hyper is in many MPNs but what gets called that seems inconsistent. Your result should have a % cellularity with it, I just asked and got mine.

These term in your result, dyserythropoiesis, I've not often seen in MPN. It does show up in this reference for MDS along with unusual granulopoiesis. I recall one member that has both MDS and MPN. Has your Dr discussed any conditions other than MPN?

<<Finding significant dyserythropoiesis or dysgranulopoiesis should prompt consideration of MDS rather than ET.>>

clevelandclinicmeded.com/me...

Also, the presence of dyserythropoiesis and dysgranulopoiesis suggests MDS in this reference:

<<MPNs are generally distinguished from both MDS and MDS/MPN, by the absence of morphologic dysplasia, which includes dyserythropoiesis and dysgranulopoiesis and monocytosis.>>

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

[artydutch in reply to EPguy]

I will check my paper work for % of cellularity. So far my diagnosis is PMF intermediate 1 fibrosis score 1-2. Are you saying I should query diagnosis? Are you a medic yourself? Anna Godfrey from Cambridge uk analysed my bone marrow and did the report. How different is the prognosis and treatment? Concerned…

[EPguy in reply to artydutch]

I'd defer to the experts, and if they have ruled out MDS that is the answer you need. I'm not medical at all, just very technical. I'm only good at finding and learning new info, trying to make sense of it, and following where it leads. I do sometimes bring what I find to my Dr to ask questions.

I don't know much about MDS, I can look into it. It seems there can be overlap and uncertainty between them:

<<Myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes are a group of chronic clonal myeloid malignancies in which there are features of both MDS and MPN at the time of presentation...Because of this overlap, there has been an inherent difficulty in the diagnosis and classification of these neoplasms>>

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

[artydutch in reply to EPguy]

I have looked at all my paperwork and mds/mpn overlap has been mentioned and offered as a differential diagnosis from my biopsy, but my blood tests did not match the diagnosis. However I will ask again how firm to diagnosis of MF is when I see my doctor next. Genetic tests are back but no appointment available until 21 on account of holidays.I do not think it effects any treatment decisions so will try to put it aside for a bit. Thanks for all your help and links to info. I have tried to understand the article and glean that with increasing genetic testing there are more ever classifications of overlapping conditions. Much was way over my head. I will let you know what the outcome of these genetic tests is.

[EPguy in reply to artydutch]

I agree with you that whatever the Dx your Dr will give you the best treatments available. I see the same in the report, more genetic info allows better information. It's a lot of probabilities in there but no certainties, as usual.

You are entitled to ask how Dr figured your Dx. I have been trying to learn more about my BMB for the exact same reason.

[hunter5582]

The testing beyond looking at the driver mutations and the allele burden is next generation sequencing looking at known non-driver mutations associated with MPN presentation. This is one example of that kind of testing. files.labcorp.com/labcorp-d...

Many docs do not look at this kind of testing at this point. However, I think it will eventually become the standard of care as the role of the genome in MPNs becomes better understood.

There is also testing looking at whether the JAK2 mutation is heterozygous or homozygous. This is only for research purposes at this point.

[charl17 in reply to hunter5582]

My specialist at Moffitt checks my non-driver mutations every couple of years. I have a favorable profile of these mutations and I believe this was the basis for treatment with interferon vs ruxolitinib. I am very happy with the results. After almost 4 years of Pegasys I am down to 45 mcg every 2 weeks. Maybe I can be done with it soon.

[Alex9621 in reply to charl17]

I hope I am not being intrusive but may I ask what doctor you are seeing at Moffitt? I am currently going there.

[artydutch in reply to hunter5582]

The results are back but am unable to get an appointment to discuss until 21 September on account of holiday leave. Frustrating. I think that not all my tests to date totally add up. I am treated at Cambridge Uk where a lot of research is going on. My consultant is also qualified as a pathologist and discusses with other pathologists. Seems like I am a medically‘interesting ‘ case, as many tests being done.

[hunter5582 in reply to artydutch]

Did you get a copy of the results yourself? Hopefully so. That way you can figure out what questions to ask in advance.

I do know about being an "interesting patient." Hence my goal to become "The World's Most Boring Patient."

[artydutch]

Thank you hunter, as always quick and informative. I should get the results soon but have a weeks holidays booked so it will now be early September. I will share what I learn.