So, I have been wondering about the difference between the various bcr/abl transcripts and the various gene mutations.
To my understanding these are two different things. Please read and let me know if I get them right:
The transcripts have to do with the breakpoints in the BCR and ABL genes, which result in different combinations of the fusion gene, and different molecular weight (?). Therefore, there are various transcripts and sub-categories:
Based on the major BCR break point (M-BCR), you get the transcript p210, and two different variants, b2a2 (e13a2) and b3a2 (e14a2).
Based on the minor BCR break point (m-BCR), you get the transcript p190, variant e2a2.
Based on the micro BCR break point (μ-BCR), you get the transcript p230, variant e19a2.
Plus, I think there are more combinations based on different ABL break points, other than a2.
Mutations. Where to begin. I have no clue what's going on here, apart from the infamous T315I, which I understand is a single base pair substitution. I have also read about P-loop mutations, and how they can affect imatinib binding, but nothing more than that.
So I have some questions towards you, guys:
1) How common are they? Not T315I in particular, but in general. If it is a not-so-important mutation, I guess it is possible that a lot of us have one, and we just don't know, right?
2) Upon DX, I was told that I have the p210 transcript, variant b3a2. I was also told that I don't have T315I. Looking back, and checking my lab results now that I know more, I don't understand where the second claim comes from. Is T315I detectable in a usual PCR test (if they know they have to look for it)? Or is mutation testing a different test?
3) Is it ok if you don't have a mutation testing upon DX? I'm 4 months into treatment after DX, and I would say I am doing pretty well on Nilotinib. Is there any reason to ask for mutation testing, if the trend of my q-PCR doesn't alarm my doctor?
4) When you get a mutation, what's the symptom? I guess, since you are tested on the transcripts that you have, and you can get the mutations on those transcripts, you will see your q-PCR rising? Is it possible that your blood test counts are affected first?
So, what's your take on the above?