Gleevec scientifically known as CGP57148 (imatinib) and formerly known as STI571 is the new member of a class of agents that act by binding using a kinase inhibitor to try to control CML. It acts as a specific kinase inhibitor, which induces complete remission in the population of those with chronic-phase CML. As a result of the treatment there are no immature cells seen in the blood, and the spleen returns to its normal size in a complete hematologic response (CHR). Equally patients using Gleevec see a dramatic reduction of their tumor clone cells, and restores normal regulatory behavior in the leukemic clone. As well as, the occurrence of a marked increase in the proportion of blast cells, this in addition leaves cells undamaged. If no cells with the Philadelphia chromosome are found in the blood or bone marrow, then patients obtain a complete cytogenetic response (CCyR).
The process by which Gleevec acts to inhibits bcr-abl in CML patients is by helping to reverse uncontrolled cell growth where Gleevec acts on a molecular target by a method that is more specific to cancer cells. It was shown that there is a substantial in vivo inhibition of the enzymatic activity of BCR-ABL at the 400 mg dose. which decreases phosphorylation of CRKL (a substrate of BCR-ABL). Since Gleevec was designed as an inhibitor of a specific receptor linked with CML, Gleevec also inhibits the Platelet-derived growth factor receptor tyrosine kinase and the c-kit tyrosine kinase.
Furthermore, because BCR-ABL is critical to the development of CML, the mutation must be eradicated from the patient and phosphorylation by bcr-abl may play a role in down-regulation of tyrosine kinase signaling.these on and off switches know to be Kinases and phosphatases are activated by such extracellular signaling molecules.
It is shown that by using a high dose of Gleevec it prevents the ABL domain from phosphorylating the tyrosine residue, which thus results in preventing the accumulation of hematopoietic cells that express bcr-abl. As a result if the bcr-abl gene is not found in the patients blood after treatment by using a PCR test the has a complete molecular response (CMR). Individual patients who were put in groups receiving daily doses of 25, 85, 140, 250, and 750 mg; of the lower doses of Gleevec administered they had no difference in the degree of phosphorylation, this gives Gleevec not much of an effect when being...