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TFR report May 2025

I had my routine PCR check in March of this year and for the first time in 4 or 5 years (I lost track) of treatment free remission with no TKI drug and "undetected", seeing a positive result no matter how small was thought provoking. I was no longer "undetected" .....

My PCR came back at " < 0.01%".

It was time for me to "believe my own research" and know that this was likely a false positive within the noise of the test. I wanted to take another bcr-abl blood draw immediately, but my Oncologist suggested I wait six weeks to verify a trend if there is going to be one. We both felt this was a fluke.

Six weeks later at the end of April, I retested and my bcr-abl came back "undetected" once again. Fascinating.

As much as I know about the biochemistry and oncology of CML - I was nevertheless "surprised" to see this "blip". A result of <0.01% is indistinguishable (statistically) from undetected in terms of the precision and accuracy of the PCR test. Still, I reacted ..... what if ....

I am confident that even if CML returned for an encore, my immune system is in far better shape than it was during those fateful days back in 2010 when I was diagnosed. There is no way CML can get break out I thought. But seeing a detection is a useful reminder to stay vigilant.

Hi Scuba

Glad to hear you are back to undetected. I'd love to see the results of BCRABL testing on a large number of the general population. I think it is likely that a few people would have very low levelsof BCRABL mutation and be unaware of it, and it would not develop.

While it would be interesting for us, I don't think it likely that anyone would fund the research.

Biernaux et al. Study: In a study conducted by Biernaux and colleagues, 117 healthy subjects were tested, and 23 were positive for the BCR-ABL mRNA, indicating a prevalence of approximately 20%. The study noted that individuals aged 20 to 80 years were more likely to express the BCR-ABL transcript, while cord blood samples from newborns showed no positive results.
JSciMed Central+1ASH Publications+1

Gambacorti-Passerini et al. Study: Another study found that BCR-ABL hybrid genes are formed and transcribed in leukocytes from more than two-thirds of healthy adults. Specifically, fusion transcripts with b2a2 or b3a2 junctions, characteristic of chronic myeloid leukemia (CML), were detected in 27% of the subjects tested. Moreover, when using an additional PCR protocol targeting the e1a2 junction, typical of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), BCR-ABL fusion transcripts were detected in the majority (69%) of normal individuals.

I have long believed the mutation(s) creating bcr-abl is "natural" and occurs all of the time which can lead to detection of the protein. But for most people, this presence likely comes and goes.

Thanks Scuba. A much larger study would be nice, but this is a LOT better than nothing.

I have come to believe that everyone "creates" bcr-abl as they age. And that the only reason some people progress to disease and others do not is because of natural immune surveillance and other factors preventing bcr-abl enhancement or the rate of bcr-abl cell production (as can happen with radiation exposure) is sudden and dramatic leading to immune system being overwhelmed. Leukemic cells express the vitamin D receptor. This causes leukemic blast cells to differentiate into daughter cells which then go through apoptosis and/or caught by NK T-cells. Low vitamin D has been documented with poorer outcomes for CML patients.

Right now the PCR test commonly used is sensitive to about 0.005%. PCR-D (digital) test is more sensitive and will pick up bcr-abl down to 0.0001%, but is not routinely used in the clinical setting (more for research purposes). I would bet many more people walking around would test positive for bcr-abl if the digital PCR test is used.