As usual I'm focused on the progression data that is sort of buried in here. See below this data for rough definitions of training vs validation cohorts.
AML progression: n (%) 5 (1.7) 2 (1.4) 3 (2.1) P=0.67
For MF Jak2 allele more than 50% takes MF progression from 4.3% to 28.5% (training) and 2.8% to 13% (validation) for
**~5X more MF risk for allele > 50%.
For AML only the Training cohort has a signif P value. In this one allele >50% leads to
**3.5X higher AML risk.
It does not cover reducing allele, and that remains a question. But reducing (via INF for example) should be better than not reducing. INF over time usually can give reductions of the size needed to get under 50%.
Still need prospective studies clearly showing this direct benefit, but more circumstantial evidence that INF may be useful.
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Here is more on the main point of the study:
My focus was elsewhere but a few details some of us may like to know about that I learned:
1- Arterial Thrombosis concerns stroke or heart attack, Venous Thromb is
for <<deep vein thrombosis, DVT (has been called economy class syndrome) , and pulmonary embolism or
abdominal vein thrombosis>>
AT is a bigger deal in the reference below. I've not been clear on these before.
2- In my very basic understanding; a Training cohort is the actual experimental group and the Validation cohort is where the lesson learned is applied to see if it holds. They used both which seems good.
Some misc thoughts on the ncbi study:
The main goal was <<we identified JAK2V617F VAF > 50% as an independent strong predictor of VT>> AT was less affected. They claim to have corrected for the other factors (which includes the way high HCTs in the >50% allele of ~HCT 54-56) I'd like to see more in here about that.
From the ref below and others, HU helps with AT but not much for VT. Maybe reducing allele to <50% can reduce VT as in the ncbi study at top here.
Hi ETguy,Thanks for this information! I recently found out my allele burden on my first test was 12%. That was in 2016 (a test my dr did and never told me!). In 2020 per BMB, it was 15% and then up to 18% this past November. I have been on HU since October 2020. I’m 63, so I feel like I am at pretty low risk of it increasing very substantially. It does appear that HU is not going to keep the allele burden in check. Is that true?
Are your alleles all by BMB? I've read that blood based can give ~4 points lower. I fit that, 14 Blood vs 19 BMB. So you need to compare same methods.
You've likely seen these plots here made from the ContiPV data. The top one suggests HU may level allele but at a much higher level than INF.
The most complete study, contiPV shows average starting alleles closer to ~40%. But this recent press release points to an advantage for starting with lower allele. I think they have data details that are not public. The lower age part also points to us (I'm 62) getting moving on it.
Thanks for posting. A lot of very interesting material.I have never had my allele burden tested - (on the basis that it wouldn't affect my treatment). I shall certainly ask for this at my next appointment.
Generally correct. But 3x neg may still have other non-driver mutations. Problem is they are still figuring out what those mean and you're right, this study did not look there.
<<Recent studies have turned their attention to triple-negative MPNs and the search for other possible driver mutations using whole exome sequencing (WES)5, 6, 7. Both somatic and germline gain-of-function mutations in non-traditional exons of MPL and JAK2 were identified, as well as cases with no mutation that showed polyclonal hematopoiesis. About 10% of cases of triple-negative ET and PMF showed mutations in exons 3, 4, 5, 6, 12 of MPL and 10% showed germline mutations in exons 8, 13, and 15 of JAK2. WES methodology is limited, however, in that it can only detect mutation(s) in the coding exons of genes, and cannot detect mutations in coding sequences at low variant allele frequency6, >>
I got 54 genes studied in the "next gen sequencing." Probably need to wait for the gen after that to really find them all... Most the ones in that mess above were not in my gene study.
Just diagnosed in December 2021 ET with JAK2 positive my dr. did not know the meaning of the quantitative value. Is that the allele #? JAK2 V617F Mutation Quant
Rslt ⁰²
POSITIVE
The JAK2 V617F mutation is detected in the provided specimens of this individual.
The formatting in the post is broken up but it appears you have ~11% Jak2 allele. That is in a common range for ET. But the exact 10.82 number is surprising since it's not normally that precise.
If your Dr does not know about this subject you should find one who knows MPN at least for 2nd opinions. Allele is known as a basic part of the MPN condition for the last 15 years.
Did you get NGS (next generation Sequencing)? This looks for other mutations that you should have in your record for future reference along with Jak2.
What does NGS stand for? The soonest I could get to see a MPN specialist is in July. I am scheduled bi-weekly with a local hematologist. Yeah I'm not sure how to interpret it "not indicated" as in not tested or not there? Yup LabCorp
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