What is the biological therapy of Chronic myeloid leukemia?
The most common treatment is a biological therapy used, a treatment drug such as imatinib also known as Glivec, over several years patients use this treatment due to the positive response and the drug maintains leukemia under control. However, imatinib won’t work on all patients. Therefore, alternative treatment drugs are used such as Ponatinib (Iclusig).
The ideal target for molecular therapy is the BCR/ABL due to the presence of the fusion protein in all chronic myeloid leukemia cells which isn’t found in benign cells. The fusion protein is essential and sufficient to develop the leukemia. 2-phenyl aminopyrimidine tyrosine kinase inhibitor is the class of compounds which imatinib belongs to. Imatinib is a potent tyrosine kinase inhibitor specifically: Abelson-related gene (ARG), KIT, platelet-derived growth factor receptor (PDGFR) α and β and Abelson (ABL). Each tyrosine kinase has binding sites specifically for ATP, this is located on the active sites. The tyrosine kinases catalysed creating the enzymatic activity which is when ATP becomes tyrosine residues, this reaction takes place in the terminal phosphate, this process is known as phosphorylation, this is shown in figure 1. The BCR/ABL has an ATP binding site which imatinib binds to, imatinib locks into a self-inhibited conformation. This prevents the protein semi-competitively from the activity created from the enzymes. This can conclude that altering the equilibrium towards a conformation which is open or active, which is caused by BCR/ABL mutations. This can create resistance to imatinib. The inactive form of BCR/ABL that is a non-ATP-binding to be stable, however, imatinib can take up the active site (TK) which can lead to a decrease in activity. The binding and stabilization allow tyrosine autophosphorylation to be avoided.