Allele Burden (this is a different question - I PROMISE!!!)

[ERei]

3 years ago my blood was tested for Jak2. The report said: "My JAK2 mutation comprises > 60% of total JAK2, suggestive of a homozygous/hemizygous mutation. Patients with this type of mutation usually have more aggressive disease."

I went on hydroxyurea in Dec 2021. My bloodwork was repeated and the report said " Low level of JAK2 V617F mutation (3.5%) in peripheral blood"

Are the 60% and 3.5% both measuring my allele burden? Are we comparing apples to apples? Is this even possible?

[EPguy]

The very different wordings suggest the tests were from different labs. Is that right? It's best to get from the same if possible.

Describing it as percent of total accurate, but maybe old fashioned, this report is from just after Jak2 mutation was discovered (2006) and uses that language: "The percentage of total JAK2 represented by JAK2-V617F (%V617F) in ET and in PV was then analyzed "

ashpublications.org/blood/a...

I just saw the ">" sign in your results. This suggests a more qualitative rather than the more precise quantitative test the gives you the precise 3.5% result. Another indication your 1st test could be more old fashioned. But it's still relevant.

So the results are for the same thing and the huge difference does point to an actual difference.

--

It is in fact plausible to see a good reduction on HU after the 1st year. The best data on this is from the Besremi study, see the plot. HU, in gray, has a large reduction in the 1st year. Yours is particularly large, but might still be explained by this result, with maybe some difference due to different labs.

Homozygous has been associated with more aggressive disease, but maybe that's simply because it's associated with higher alleles. It is more common at the higher alleles often seen in PV. But there is a pleasant trade off, homozy also tends to respond well to IFN (Pegasys or Besremi). These have been discussed in prior posts.

If you stay on HU you'll want to keep up the Jak2 tests. But it may be a good idea to discuss IFN with your Dr for best odds of long term reductions.

Ropeg5+Years

[ERei in reply to EPguy]

Thanks for your response. Both tests were done at the same lab (NeoGenomics) and the tests were done approximately 2.5 years apart. I actually stopped the HU about a month ago - I couldn't take the constant nausea anymore. (I originally thought it was due to my reflux but when I stopped the HU it went away) Since my allele burden is only 3.5% I was thinking I'd hold off on besremi.

[EPguy in reply to ERei]

If your blood counts are/stay good, going off therapy seems reasonable, esp the HU since you're not tolerant of it. Has your Dr given an opinion on the plan?

But assuming bloods stay good, you'll want to watch the allele carefully if you're concerned about its level. For most of us (not all) it naturally increases over time without some intervention even if bloods stay ok.

[EssThro]

It sounds like you should talk with your doctor to get a definitive interpretation and treatment plan. Good luck to you!