Imatinib is successful in treating BCR-ABL-positive chronic myelogenous leukemia (CML) patients. This is achieved by suppressing the expansion of BCR-ABL-positive bone marrow cells present in the patients. Besides BCR-ABL, imatinib also inhibits KIT, a receptor tyrosine kinase that can be activated by BCR-ABL and a positive regulator of expansion of bone marrow cells. These results complicate the interpretation that inhibition of BCR-ABL by imatinib is responsible for the observed efficacy in patients.
Please describe an experiment, with appropriate controls, that uses a chemical-genetic approach to address the question of whether inhibition of JUST BCR-ABL by imatinib is sufficient for the observed suppression of BCR-ABL-positive bone marrow cells.© BrainMass Inc. brainmass.com October 10, 2019, 8:15 am ad1c9bdddf
Let's firstly break down the issues and identify the goal of the study:
BCR-ABL+ bone marrow cells contribute to leukemia in CML patients.
BCR-ABL activates KIT, KIT is also a positive regulator of bone marrow expansion
Imatinib inhibits BCR-ABL
Imatinib also inibits KIT
Imatinib decreases measures of leukemia aggression in CML patients
With this info, we can effectively rephrase the research question into something more specific:
Does imatinib do so via BCR-ABL inhibition independent of KIT, or is KIT vital to the efficacy of imatinib in decreasing CML aggressiveness depend also on KIT functionality?
To do this, what a researcher might have to do is design a CML model wherein KIT can be ...
An example of how a chemical-genetic study design could help elucidate whether protein KIT is vital to BCR-ABL induced bone marrow expansion in leukemia.