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Importance of different break points detection values on PCR


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#1 Melanie

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Posted 26 April 2016 - 05:54 PM

Is there more weight given to the detection value of b2a2 % vs the b3a2? Just wondering if one break point is harder for the TKI to work on then the other. I know you add the two together to get your total PCR. My most recent "local" (I have PCR test done at 2 different labs) PCR results has the b2a2 declining from .021 to .007, but the b3a2 ticked up to 0.126 from 0.059. Total now at .14, which is up over all. A little concerned and hoping that b3a2 doesn't carry as much importance as maybe the b2a2. Silly question maybe...but I can dream! 

 

Thinking this turtle took a few steps backwards...


Dx - 05/2011; PCR: 15.04; Fish: 87% Slow responder due to pancytopenia. Current - Bosulif - Nov: 2012, Mar 2016 lowered to 300 mg. 07/16 back to 400 mg. Clinical trial drug, Promacta, Feb 2013, for low Platelets.
CyCR - Aug 2014, Positive for 1 chromosome Sep 2015. PCR: 12.77 in Oct, 2012 to 0.04 (MDA) in Mar, 2016. 4/2016 - 0.126 (Local lab (IS); 05/2016 - 0.195 (local); 6/2016 - 0.07 (MDA); 7/2016 - 0.03 (local) 9/13/2016 - 0.16 (MDA); 9/26/2016 - 0.31 (MDA); 11/2016 - 0.012 (local); 01/2017 - 0.24 (MDA); 04/2017 - 0.09 (MDA); Cytogenetics show der(1:7)(q10;p10)7 chromosome mutation. Repeat of Sep 2015. PCR - 6/2017- 0.035 (local); 10/2017- 0.02 (MDA)

#2 Trey

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Posted 26 April 2016 - 08:47 PM

The b2a2 and b3a2 are given equal weight since they are the two most common breakpoints (99%).  Some studies show b3a2 responds better to TKI therapy, but other research shows the opposite.  So it seems to be a draw.  But either can cause CML and are equally bad if left unchecked.  So one is not "more friendly" than the other.

 

But it is a matter of ongoing interest whether one or the other is more aggressive, more prone to mutations, allows more cessation success, etc.  There is not even an understanding about how they both arise at the same time.  Two translocations?  A translocated translocation?  Retrodifferentiation?  Transdifferentiation?  (Not that there's anything wrong with that.)  There is very little data on those issues. 

 

If you have both at the same time they are like evil twins.  Twisted sisters.  Each has its own disturbed personality.  Like Evil Chucky meets the Bad Seed.  They do not act in tandem. 

 

Overall, both must be controlled.



#3 Melanie

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Posted 27 April 2016 - 03:30 PM

Thanks Trey! You always make me laugh! 

 

Guess, I never paid much attention to the different breakpoints and mainly focused on the total PCR result.  It would be nice to know if one is more dangerous than the other, like most evil twins. Not that there's anything we could do about it, but sometimes the information is in-powering. I like to visualize my TKI beating up the evil ones to get them in control.  Maybe now, I'll name them...something appropriate for the bullies they are. I like Chucky for the b3a2...I'll have to think of a name for the b2a2, since it's on the run.

 

Don't most people with CML have two or more breakpoints on the chromosomes? My results describe the b2a2 and b3a2 as being major breakpoints and e1a2 as a minor breakpoint. Does major or minor mean anything in regards to burden of leukemia? Can the margin of error be in each breakpoint or is it calculated for the total?

 

Always learning...


Dx - 05/2011; PCR: 15.04; Fish: 87% Slow responder due to pancytopenia. Current - Bosulif - Nov: 2012, Mar 2016 lowered to 300 mg. 07/16 back to 400 mg. Clinical trial drug, Promacta, Feb 2013, for low Platelets.
CyCR - Aug 2014, Positive for 1 chromosome Sep 2015. PCR: 12.77 in Oct, 2012 to 0.04 (MDA) in Mar, 2016. 4/2016 - 0.126 (Local lab (IS); 05/2016 - 0.195 (local); 6/2016 - 0.07 (MDA); 7/2016 - 0.03 (local) 9/13/2016 - 0.16 (MDA); 9/26/2016 - 0.31 (MDA); 11/2016 - 0.012 (local); 01/2017 - 0.24 (MDA); 04/2017 - 0.09 (MDA); Cytogenetics show der(1:7)(q10;p10)7 chromosome mutation. Repeat of Sep 2015. PCR - 6/2017- 0.035 (local); 10/2017- 0.02 (MDA)

#4 Trey

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Posted 28 April 2016 - 03:43 PM

Having two is fairly rare, less than 5%.  Most have either b2a2 (e13a2) or b3a2 (e14a2).  I have two (b2a2 and b3a2) and have done very well.  Some here have either b2a2 or b3a2 plus e1a2.

 

Major breakpoint only means they break at the major breakpoint cluster region (b2 region) and they are also called P210.  They are nearly 99% of all Philadelphia chromosomes.  The e1a2 is a minor breakpoint region Philadelphia chromosome break, breaking at the e1 region and is called P190.  There are also very rare micro breakpoint cluster region variants called P230.  Major and minor have nothing to do with leukemic burden or aggressiveness of the breakpoint.

 

http://www.ncbi.nlm..../pubmed/9376660

 

The b2a2 seems to result in higher WBC at diagnosis, and b3a2 seems to result in higher platelets at diagnosis.

 

http://www.haematolo...ntent/99/9/1441






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