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Why does the BCR/ABL % decreases rapidly first and then the decrease slows down?

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My BCR/ABL went from 50.2% at diagnosis to 1.7% in just 10 weeks, but in the last two months the reduction is only from 1.7% to 0.233 %. The logic should be that having less CML cells in your blood make it easier for the TKI to destroy them unless the problem is that the TKI is less efficient at that level.

Hi vlacer

This is an interesting question and I think about it differently to you - to me it is logical for the TKI to struggle to kill off the few remaining cells when BCR-Abl is at a low level.  I think about this in terms of an analogy.

Suppose you're trying to get rid of a massive locust plague in a field.  Armed with insecticide, you enter the field and spray every plant in sight.  Since the field is so completely infested with locusts, almost every drop of spray hits its target and kills the pest, so you're able to reduce the infestation from 50% infested to only 2% infested in a short time.  But now these little guys - the few that survive - are on to you and are able to hide in the places where they were when the spray couldn't reach them.  They try to multiply, but the next salvo of spray hits and kills their offspring, as well as those unlucky enough to stray from their hiding place.  They are also now so few and far between that the majority of the insecticide doesn't hit its target... but you have to keep on spraying every day to prevent the offspring from multiplying. 

The locusts are, of course, analogous to the leukaemic cells and the insecticide is the TKI.  I've read that some of the leukaemic stem cells are called "quiescent" because they are able to hide from the TKI - eventually, though, they wear out and lose the battle!

So that's my very unscientific explanation, but I believe it is supported by some of the research.  I'm sure that many of the more knowledgeable members on this site will provide a better answer to your question!

Best wishes for your ongoing recovery

Martin

Hi Martin,
Thanks for your reply. I was diagnosed 5 months ago thanks to a blood test after COVID 19 infection, so I am trying to learn as fast as I can about CML and this Forum is a great place to find answers.

I agree with your analogy, but I would expect that to happen only after you are "undetected" or at least after MMR and I am not there yet. I would think that until then, the TKI should be able to inhibit the tyrosine kinase that is made by the BCR-ABL1 gene in the dividing leukemic cells regardless where they are.
I learned about Leukemic stem cells, that can remain dormant for years in a very interesting post from Scuba about fasting for 3 days, which I am planning to do