In CML patients it has been observed that BCR-ABL mRNA shows decline in response to Gleevec treatment.
Dear Chandra,
The Fused protein of ABL and BCR is inhibited by Imatinib and as a result the proliferation of immature malignant cells with BCR-ABL is inhibited as well. This will result in dominance of normal cells and eventually undetectable level of BCR-ABL in blood but we believe that the malignant stem cells will remain in bone marrow and the cessation of therapy with Imatinib can result in relapse of the disease, the same event is observed in Imatinib resistant patients which the drug cant inhibit the BCR-ABL with mutant TK domain.
Yours,
Heidar
As far as I know, patients become resistant because Abl mutates in the kinase domain (eg. T315I or other) and imatinib is not active any more. About mRNA I agree with Heidar.
Heidar's answer is correct. As with most (if not all) chemotherapeutics, if you use it, you will lose it... or, if you use an agent, on a long enough timeline, any malignancy cell's will change in such a way to resist the treatment. You have to start somewhere.
All the above answers are correct. The simplest answer to your specific question is that in absence of or by blocking the specific activity of the mutant TK, the CML cancer cells die. Thus you see a decline in the mRNA in total blood after Gleevec treatment.
Agree with most of the comments, but want to also mention that imatinib resistant clones frequently precede imatinib treatment. We witness an enrichment in pre-existing imatinib-resistant clone(s). This hypothesis received quite a bit of attention over the last few years (see de-novo hypothesis)
AC - is this because you have two hit and three hit non-solid tumors? (More than one translocation, amplification, rearrangement)
There is limited data available. In AML, the "two-hit hypothesis" of leukemogenesis implies that AML is the consequence of at least two mutations, one conferring a proliferative advantage (class I mutations) and another impairing hematopoietic differentiation (class II mutations) - see
http://www.uptodate.com/contents/pathogenesis-of-acute-myeloid-leukemia
I remember that at AACR 2012 or 2013 one group presented a very interesting array approach supporting this hypothesis
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