BMB conflicts blood test result on JAK2

[Bindi77]

My 22 yo old had a DVST which started us down the path of determining why he got the clot and if there are any underlying conditions. Initially in hospital his blood test showed a below 1 percent of JAK2. His RBC and HCT were at high end of normal range. Many other tests were run including spleen US. All came back normal. A new doctor decided to run JAK2 again and came back right at 1 percent. Next step was for bone marrow biopsy which I have been told it can be and also that it can not be telling definitively of an MPN. The most confusing part is that his BMB shows no JAK2 detected..????? How can this not be detected but show up in 2 blood tests (although low levels). Also the rest of the BMB results show favorable- It has been so confusing. Anyone have any similar results? Or any input on this? Thank you

[Lappool]

This disease never has anything clear cut & blows my mind. You’ll see somehow people in this group with no mutations at all & a normal bmb, and EPO but still have PV. You’ll see people who have negative jak2 in blood, but positive in bone marrow, you’ll see negative jak2 in blood and bone marrow & low EPO. This disease has blown my mind in many ways. There seems to be so many ways to be diagnosed as opposed to just wishing there was a clear cut way of diagnosing a condition right? Then there’s the whole secondary polycythemia, which is a whole different entity. Anyways, has your sons EPO levels been tested?

[Bindi77 in reply to Lappool]

I agree and this makes it all that much harder to accept a diagnosis. Yes his EPO was good. Thank you so I don’t think I’m going crazy I’m relieved to know I’m not the only one who feels the way you do

[Lappool in reply to Bindi77]

Trust me, I’ve been battling with this for almost 6 months now after a routine CBC showed some elevated values. My heam seems to think it’s because I live at high altitude. My EPO was tested & it was normal, but I have no JAK2 mutation, normal iron levels, normal ferritin, normal b12, normal RDW, normal platelets etc. I’ve heard from 2 heams that I don’t have it, but then you’ll read in this group, “but was he an MPN specialist???” It’s crazy to think that a BMB can make it even more confusing 😂Sorry to hear about your son & I hope he’s doing better

[EPguy]

The Jak2 levels can be different in blood vs marrow. Mine were 5 points different, higher in the marrow in my case. So at 1% blood, these differences could explain the zero BMB result.

There is a condition known as CHIP, where there can be no overt disease and very low allele burdens but some increased risk of PV or other conditions developing.

This doesn't mean your son has this risk, only that it can be checked.

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

Has your son had the full gene sequence? They look for all the other genes related to blood diseases. For example in addition to Jak2 there are DNMT3A, TET2 as in this report, and many others that are checked. I had 54 checked, they do more than that these days.

If you get regular checks, it's most common to use just blood as it's easier and compares the same type of source.

[Bindi77 in reply to EPguy]

thank you for your reply and very interesting that you had differing results between blood and BMB also. One specialist that I had a conversation with did also mention CHIP. I am not sure if they did a full gene sequence. I know they checked the more common ones. I feel like it was maybe only JAK2 and one or two others. I will definitely ask about that though bc that has been a question I have pondered (could there be other mutations ?) Thank you again for this info. Was it an MPN specialist that ordered the full sequence bc I feel like some hematologists are reluctant to order some of these less common tests?

[EPguy in reply to Bindi77]

My 1st Hem was not MPN specialist but he did a good job getting my Dx sorted. It's in the UCLA Health system which has great resources.

[Bindi77 in reply to EPguy]

I just checked and they did run an NGS panel checking for all the genes relates to blood disorders. 👍🏻

[Bindi77 in reply to EPguy]

Hello and I just read through and “attempted to understand” the link that you sent regarding CHIP. Am I correct in thinking a diagnosis of CHIP could potentially be a worse diagnosis than PV alone? It seems like CHIP can be a diagnosis on its own or in conjunction with other diseases like PV? Do you know?

[EPguy in reply to Bindi77]

CHIP by itself can indicate an increased risk for PV but is not a Dx of PV. So it is a lower risk than an actual Dx of PV. But whether it leans toward any sort of MPN depends on which genes were found according to this report.

In MPNs it says "the three most common implicated genes are DNMT3A, TET2, and ASXL1" Others they note are "TP53, JAK2, SF3B1, GNAS, PPM1D, and BCORL1". But this 2nd set includes other conditions beyond MPN. (Jak2 is implicated in CVD, PV, atherosclerosis aggravation table 1)

The article also says "the cutoff used for VAF has been set at 2% for the diagnosis of CHIP" So his 1% does not meet that. But it also discusses newer more sensitive tests.

So it could be CHIP with that 1% Jak2. But maybe not related to MPN, rather one of those other conditions. Has he checked ok on a full cardio workup?

Conversely I and many others have only Jak2, so those three above (DNMT..etc) are not required to have MPN.

The Jak2 rising from less than 1% to 1% does not yet mean it's increasing since it's likely different labs and at these low values there will be large variations on a tiny number. But it makes sense to me to he should get periodic Jak2 tests to track any ongoing increase.

There are Drs who advocate starting IFN (interferon) early esp for the young to prevent disease, but in his case I expect Drs would wait to see whether an MPN is actually indicated and/or the Jak2 rises.

They list risk factors for CHIP (beyond the main one of age) as "C = chemotherapy, R = radiation, I = inflammation and infection, S = smoking and male sex"

Of course this is way more complex than this one CHIP report.

[Orangeboykitty]

If your son had any of the covid vaccines, blood clots are a known side effect. It may have nothing to do with a MPN, especially if multiple tests haven't shown anything.

[Bindi77 in reply to Orangeboykitty]

Thank you for your reply and I wish that could be the explanation but he did not have any Covid vaccines. Several doctors did ask that as well

[Wyebird]

hi, welcome

I’m not medically trained so my answer is from what I’ve learnt over the yrs.

The blood test will detect a mutated gene. Jak2 is one such gene.That along with blood results will determine your MPN.

Some people are classed as triple negative.

This means that the blood test indicates abnormalities but no defective gene present.

New mutations are found periodically.

I’m Calr ET. I believe Mpl is more recently found.

BMB will show what’s happening in the bone marrow and could well appear normal if the illness is in its infancy. A few years down the line it could be repeated and the comparison significant.

In others a BMB could be significantly abnormal.

We are all so different.

10 yrs since diagnosed and I’m still learning.

You will find this site extremely useful. You want the best for your son and so your mind must be in a turmoil. No matter how small or insignificant the question maybe ask away. There will be someone here to support you and offer and explanation.

Alternatively go onto mpnvoice.org

It’s a charity for people with MPN’s run my amazing people.

It will give you lots of information and support.

[Bindi77 in reply to Wyebird]

thank you for your reply. When you say “… blood test indicates abnormalities but no defective gene present”, what would abnormalities be? I am trying to understand that sentence. I was told by one MPN specialist that they would completely expect the BMB to come back normal and that could be if the disease is in infancy like you said. My concerns would be if the doctors want to start him on any drugs at such a young age. This is definitely a very tumultuous time. Thank you for all your support and advice it is so helpful.

[Wyebird in reply to Bindi77]

hi abnomailities as in blood cells being out of normal range.

Make sure you get a copy of all blood tests.

The results will indicate what level your son has then what normal range would be

Eg platelets 800 but normal depending on where you live would be between 150-400

If you have a copy you can then track and ask questions.

Is that ok?

[Bindi77 in reply to Wyebird]

I understand now and yes I do track that. Thank you

[ainslie]

it’s maybe a question to ask a MPN expert, I have been told by my local Haem that NGS can be more efficient from marrow as opposed to blood, not certain what efficient meant but have also heard similar on other forums. Your son is young and there is a long time ahead so maybe wise to see an expert and then from time to time who can keep your normal Haem going in the optimum direction.

[Bindi77 in reply to ainslie]

thank you for your response. Sorry for my ignorance but what is NGS?

[ainslie]

Next Generation Sequencing , I haven’t seen one yet but trying to get one done, it as far as I know lists any mutations one has and what % each one is. Perhaps anyone with one at hand can expand that reply.