3 replies to this topic

[Melanie]

I know most PCR test for the most common breakpoints such as the p210 b2a2, b3a2 and p190 e1e2. My question is can you only have one breakpoint, say the b3a2, and then another one pops up in a later test, say the b2a2, and now your total PCR has taken a slight bump up? Do these breakpoints change during the course of treatment from having just one breakpoint detected to two or vice versa? As the disease is closer to MMR or deeper response, do the break points decrease or increase as the CML fights to stay alive?

[Trey]

A person can have multiple breakpoints.  This occurs in about 5% of CML patients.  Why it occurs is a mystery, since it is essentially having CML twice at one time (not quite, but close enough).

 

The PCR result is the sum of the two breakpoint percentages.  At diagnosis I had two (b2a2 and b3a2), and the b2a2 was higher.  Within a couple months my b2a2 was lower than my b3a2.  At 4 months the b2a2 was undetectable.  At 8 months both were undetectable. 

 

Statistics show that b3a2 (e14a2) responds more quickly than b2a2 (e13a2).  For me that was not the case. 

http://www.ncbi.nlm....les/PMC2754951/

 

It is likely that the breakpoints will respond at different rates.  Possibly one may become more difficult to control over time than the other.  One could be resistant to a certain TKI drug, while the other might respond well.  One could harbor kinase mutations, while the other might not.  So they can act independently.

 

Whether a person could be diagnosed with only one breakpoint, and then another show up later, that is possible but very rare.  Would it be a mutation of the first Philadelphia Chromosome, or the previously unidentified recessive breakpoint coming to the forefront later than the first (i.e, slower to become detectable), or a second case of the disease?  No one knows.

 

Is this a theoretical question, or do you have such an experience?  I assume you do not have this experience, but are searching for an answer as to why your PCRs do not drop more quickly, and even bounce around.

[Tedsey]

I was first dx with b2a2, then six months later, at a new doctor and a third lab, e1e2 (p190) showed up.  However, I think p190 was always there and was missed by inferior labs with inferior machinery.  I have always been suspicious that my first PCR was run by a reluctant pathologist or assistant who was stuck in a children's hospital lab over the Thanksgiving holiday (when I was dx almost six years ago).  It appears when I was dx, the pathology dept. for adults at the university hospital was on vacay, so they sent the blood sample to the children's hospital across town.  Sadly, the children's hospital lab could not quantify the leukemic load at dx.  My 2nd PCR was done later at the "adult" lab (different machine), but they still did not discover the p190.  Also, the university hospital lab had their own crazy numbering system for reporting percentages of bcr-abl.  I was so grateful that at the second doctor (and third lab) when they began to report in IS--unbeknownst to my hem/onc--I had to let her know, (bless my BIFs on this board for all they have taught me and LLS that provides a space for this forum ).  She was writing out all these crazy calculations about what MMR was and how I was way off the target (she did not understand log reductions), but this is all beside the point.  I think sometimes dx is also like a blood draw, the accuracy of the PCR (which is an average anyway), depends on the time, day, person, vile, and machinery on which testing is done.  I truly hope with all my heart my experience was an anomaly, but you cannot leave these kinds of variables out of the equation.

[Melanie]

Trey, I ask because in reviewing my PCR test, sometimes the results report both major breaking points and sometimes just one. Could be a lab reporting irregularity, but I've had the same labs for the last 3 years. It seems the b3a2 is always present, while the b2a2 comes and goes, with the b3a2 always detected at the higher %. I've had other mutations show up over the years that eventually disappear completely. I was trying to get an explanation from my doctors but it appears they're in summertime vacation mode.

My thoughts were that the Mother stem cell was trying different offenses at random times to try and trick the TKI. Maybe the reason for the TKI's effectiveness and fluctuating PCR results or plateaus. I know some TKIs are more effective with certain break points than others and wondering if there's much experience or data on it. Could taking two different TKIs give a better response for those that struggle getting to MMR or undetected? Are some LSC more intelligent, therefore more aggressive, than others? We know they're smart enough to retreat into hiding deep in the marrow, so why do some become more aggressive than others? What triggers their reappearance or makes them stay hidden?

Guess I'm just trying to find the answer to the big "why".