Abstract

Chronic myelogenous leukemia (CML) is a hematopoietic stem cell disorder which arises due to translocation of ABL gene on chromosome 9 to BCR gene present on chromosome 22. This produces BCR-ABL oncogene which is the main cause of CML. Imatinib mesylate has been the choice for the treatment of initial chronic phase of the disease. However, through BCR-ABL gene over expression, kinase domain mutations, importantly T315I CML cells acquire resistance to imatinib and other second-generation tyrosine kinase inhibitors. In this mini-review, we will be analyzing the normal functions of c-Abl and the aberrant signaling pathways activated upon its loss of regulation. The causes of drug resistance and some of the possible routes to combat drug resistance is defined. The natural compounds and their significance in drug discovery and the efficacy of tyrosine kinase inhibitors by combinational treatment with natural compounds to overcome the adverse side effects and drug resistance also examined.

Keywords: Chronic myelogenous leukemia (CML); BCR-ABL; Imatinib; Drug resistance; Natural compounds; Tyrosine kinase inhibitors