Sensitivity of driver mutation tests for CALR and MPL - not sure if I'm confident

[cmc_ufl]

Possible ET triple-negative. Mildly elevated platelets (429-455) for 10 years. All 3 driver mutations came back negative.

Spoke with my MPN specialist about the driver mutation tests I had done (from peripheral blood). He told me that the JAK2 allele sensitivity was 0.1%, meaning any allele burden above 0.1% would come back positive. I am very confident in this test.

However, the CALR allele sensitivity is 6%, and the MPL allele sensitivity is 20%. This means any allele burden less than 6% for CALR and less than 20% for MPL would not be picked up and would come back as a false-negative.

I've seen people post in this forum having allele burdens below these thresholds. Given my mildly elevated platelets, I would suspect my allele burden to be pretty low.

Should I trust these test results or ask if there's another, more sensitive assay he can run? These tests were ordered through Mayo Clinic.

[Dazakella2010]

I think you can trust the tests that are being carried out..... I think if you have to really go looking for medical problems and go digging deeper into things maybe they are not really there to begin with if that makes sense?

[cmc_ufl in reply to Dazakella2010]

I would like to think that, but there are many people on this forum with an allele burden less than these values. It is also not as clear-cut for us who have elevated platelets with no verified driver mutations.

[Dazakella2010 in reply to cmc_ufl]

By looking at you platelet levels they seem to be within normal range?

[cmc_ufl in reply to Dazakella2010]

They fluctuate in and out of the normal range.

Besides, there’s a push to lower the ET diagnostic threshold below 450. There are many people on this forum with platelet levels between 400 and 450 at diagnosis.

[PrinceA in reply to cmc_ufl]

My platelets fluctuate in similar range - dont have diagnostic yet

[cmc_ufl in reply to PrinceA]

You tested positive for JAK2 and aren’t diagnosed yet?

[PrinceA in reply to cmc_ufl]

yes not yet, PV ruled out since my EPO is normal, specialist said diagnostic can be done with only bone marrow biopsy and she didnt think I needed one at this stage since I dont have symptoms and based on age (48) considers low risk - so currently only on aspirin 4 days a week.

[cmc_ufl in reply to PrinceA]

What is your platelet history? Were they always this elevated or did they jump to this level at some point?

[PrinceA in reply to cmc_ufl]

No there were not always elevated. looks like it started in last 3-4 years ..

[cmc_ufl in reply to PrinceA]

What are your platelet levels now?

[PrinceA in reply to cmc_ufl]

the last test I had last week was 455, 447 in December and 450 in November.

[PrinceA]

Hello, my allele burden is 2.17 but it was for JAK2 V617F and the sensitivity is 1%. so if the sensitivity was 6 or 20 it would show as negative. You can ask that question to specialist and see what he thinks. My guess is that might be whats available for CALR and MPL since you did it in Mayo Clinic

[cmc_ufl in reply to PrinceA]

Thanks for your reply. I’m pretty sure I’ve seen people on this forum with CALR allele burdens below 6%, so there must be better assays out there. Not sure why it is 6% at Mayo.

[hunter5582]

There do appear to be differences in assay sensitivity. Here is one example."This assay has a sensitivity to detect approximately 10% population of cells containing the MPL mutations in a background of nonmutant cells. "

labcorp.com/tests/489150/mp...

You may want to look around a bit if you really want to rerun your labs.

Perhaps contact Intelligen Oncology - Labcorp regarding the MPN Myeloid Panel they offer to see what the sensitivity for the driver mutations actually is in this comprehensive assessment (it may not be the same).

files.labcorp.com/labcorp-d...

[Indigo42916]

I am MPL, and it was detected with allele at less than 10%.

[cmc_ufl in reply to Indigo42916]

Thank you for sharing