核医学与放射治疗

Systemic Review on Chronic Myeloid Leukemia: Therapeutic Targets, Pathways and Inhibitors

Abstract

Himansu Kumar, Utkarsh Raj, Saurabh Gupta, Rashmi Tripathi and Pritish Kumar Varadwaj

Chronic Myeloid Leukemia (CML) is a stem cell disorder, characterized by the translocation of 9th chromosome of Abelson (ABL) gene to the 22th chromosome of breakpoint cluster region (BCR) gene. Consequently, translocation results into the chimeric oncogene BCR-ABL which encodes the BCR-ABL oncoprotein. CML is mainly a disease of adults but it can occur in any stage of life and it accounts around 15% of the all the types of leukemia. Various methods have been used to combat this disease like Chemotherapy, Radiation therapy; tyrosine kinase inhibitors etc., Imatinib as a tyrosine kinase inhibitor has dramatically improved the survival rate of CML patients, hence can be referred as first generation drug against the CML. Later on, recurrence of the disease in some treated patients has also been seen probably due to mutation in oncogenes. Researchers have started to find out more efficient tyrosine kinase inhibitors which can work on mutated oncoprotein and which can be referred as second or third generation drugs. In this review, special emphasis have been given to the carcinogenic mechanism of abnormal fusion of the BCR-ABL genes, current therapeutic options to prevent this disease, and Systems Biology approach to explore the CML associated biochemical pathways. Various advantages and disadvantages of the all therapeutic options to combat CML have also been discussed.