Chronic Myeloid Leukemia: A Paradigm of Successful Targeted Therapy

Chronic myeloid leukemia (CML) is commonest type of chronic leukemia in India. It has achieved enormous attention in the medical literature because of the delineation of its molecular basis and the discovery of successful targeted therapy in the form of tyrosine kinase inhibitor, imatinib. Chronic myeloid leukemia is defined as a myeloproliferative disease that originates in an abnormal pleuripotential bone marrow stem cell and is consistently associated with a Philadelphia (ph) chromosome and/or the Bcr-Abl fusion gene1. The era of significant discovery started in 1960 when Nowell and Hungerford first observed the occurrence of small chromosome 22 in CML patients (philadelphia chromosome)2. In 1980, a reciprocal translocation was identified between chromosome 9 and chromosome 22 that leads to juxtaposition of c-abl oncogene and break point cluster region (BCR). The BCR/ABL gene product has tyrosine kinase activity which is responsible for the initiation and maintenance of malignant transformation of hemopoietic stem cell3,4.