Chronic myeloid leukemia ( CML ) exemplifies importance of molecular pathways and their exact role in oncology. Imatinib mesylate, first tyrosine kinase inhibitor (TKI) introduced into clinical practice has an ability to bind ATP – binding pockets of the ABL kinase domain. This subsequently prevents the change in conformation of the protein to the active form of the molecule, leading to subsequent death of target cells. These domains are amenable to mutations and such mutations can lead to imatinib resistance.
Multiple clinical trials, such resistances have been frequently encountered ( approximately 50-60 %) of patients. Clinical resistance is the hallmark for checking any underlying mutations. This fact is enough to speculate that such mutant clones might be present even before the start of therapy and might be pre-existing. Imatinib selects sensitive clones and thus resistant…
