Dear Confused, Curious, and Cynical Readers,
Most Oncs do not know much about CML. That's OK for most people, since the drugs do the real work. But if you ask the Onc about low dosage TKI they will reply like a robot that it could cause mutations. But what proof of this exists, Gentle Reader???? None. So how does any urban myth begin? Who knows, but repetition does not turn sharts into ice cream. Believe me, I have tried. I have even taken a pilgrimage to Brenham. No luck.
Cell hierarchy charts will not reveal any clues into this issue. And since Kinase Mutation Tests cannot detect mutated leukemic cells below roughly CCyR levels, the test is often inaccurate unless the mutated cells are the primary leukemic cell type, which often only happens at a sudden 1 log increase plus loss of CCyR. Miss Cynic has provided a good explanation of the other factors involved, so I shall not repeat the psychology into why Oncs do what they do.
I present the following factoids for your consideration:
1) The NCCN CML Treatment Guidelines authorize low dosage TKI drug dosages.
2) Leading CML Oncs regularly authorize reduced TKI drug dosages (Dr Cortes at MDA has patients such as our Michael on 15% dosage -- is he trying to induce mutations to perform some evil experiment? If so, can we watch?)
3) Dr Druker has changed from worrying about low dosage TKI drugs a few years ago to authorizing low dose Gleevec for long term "maintenance therapy" after several years PCRU, as reported by one of our members here.
4) Most kinase mutations occur while patients are taking full dosage TKI drugs (from what I have observed on this L&L website).
5) There are over 100 known kinase mutations, and most do not prevent the TKI drug from working, although they can sometimes reduce effectiveness, and only a very few can prevent the TKI drug from working.
6) Our TKI blood level concentrations change all day long. Peak concentration occurs a couple hours after taking the drug, then it declines continually until the next dose. So aren't we all on "half dose" or less most of the day and night? Why isn't that a problem if the theory of low dosage mutation applies?
If your Onc remains unconvinced, ask him to explain why TKI drugs and antibiotics act the same way to cause "mutations" (hint -- they don't, and "mutations" are not all the same).