Genetic Basis of Chronic Myeloid Leukemia

Chronic myeloid leukemia is a malignancy characterized by proliferation of myeloid series of hematopoietic stem cell. It is characterized by an initial chronic phase followed by an accelerated phase leading to a late blast phase which happens 3-4yrs after the disease onset. It was initially believed that CML is a three step process 1 but Jeral P.Radish proposed that it is a two-step process , with new gene expression changes occurring early in accelerated phase before the accumulation of increased numbers of leukemia blast cells. The chronic phase is characterized by accumulation of myeloid progenitors and mature cells in blood and extramedullary tissues. The blast phase 2 shows a maturation arrest in myeloid or lymphoid lineage. The only cure for this disease is allogenic stem cell transplantation if given in chronic phase but the therapy itself is a complex and potentially toxic modality. Treatment with Interferon α delays progression of the disease to blast crisis and in 10-20% of patients results in complete remission. Blast crisis is highly resistant to treatment, often leading to death secondary to complications like infection or thrombosis. The beginning of the use of Interferon as treatment for CML started in 1983 after a report by Tapez et al which proposed that leukocyte IFN induced 3 cytoreduction in CML . This proposal was approved by certain other 4,5,6 studies