| Chronic myeloid leukemia (CML) is a malignant disorder of human hematopoietic stem cell, accounting for 20%-30% of all adult leukemias and about 1/105 of the world population every year. It takes the third place after acute myeloid leukemia and acute lymphoblastic leukemia according to the incidence in China. The common clinical manifestation of CML. is fatigue, marasmus, granulocytosis and splenomegalia. The natural course of CML lasts 3-5 years and it can be divided into chronic period, accelerating period and blast crisis period. Clinically, chronic-phase CML does not represent a major management problem because the elevated white blood cell count is readilly controlled with cytotoxic agents in most patients, and neutrophil and platelet functions are largely normal. However, the disease progresses inexorably to acceleration and blast crisis, often within 5 years of diagnosis. More than 70% of the patients die from the blast crisis, myelofibrosis or asthenia in the end. With more and more serious environment pollution and application of radioactive weapon in the war, the incidence of CML hasbeen increasing rapidly and CML has become a common malignant tumor that threatens people's lives.So far, there is no effective treatment to put the majority of CML patients under control. The traditional treatment such as chemotherapy can not change the disease course of CML. a -interferon can only make 10%-30% of patients with CML remitted in cytogenetics for a short period. Allogeneic bone marrow transplantation is considered currently to have the greatest potentials to cure CML, but only 20%-30% of patients have the chance to accept this kind of treatment because of the requirement for patient age, the condition of donor, and the risk of such serious complications as GVHD and infection with regard to bone marrow transplantation. Though having fewer complications and no limitation in age, autologous bone marrow transplantation has a high rate of relapse because there is no effective method to purge residual leukemic cells and therefore it has poor treatment result. Perhaps the most exciting of the molecularly designed therapeutic approaches was brought about by the advent of signal transduction inhibitor(STI), which block or prevent a protein from exerting its role in the oncogenic pathway. Because the main transforming property of the BCR-ABL protein is effected through its constitutive tyrosine kinase activity, direct inhibition of such activity seems to be the most logical means of silencing the oncoprotein. To this effect, several tyrosine kinase inhibitors have been evaluated for their potential to modify the phenotype of CML cells. The most promising of these inhibitors is the 2-phenylaminopyrimidine STI571 (foremly CGP57148B; Novartis Pharmaceutics, Basel, Switzerland), which specifically inhibits ABL tyrosine kinase at micromolar concentration. Inhibition of the BCR-ABL kinase activity by this compound results in the transcriptional modulation of various genes involved in the control of the cell cycle, cell adhension, and cytoskeleton organization, leading the Ph-positive cell to an apoptotic death. STI571is the molecular-targeted drug in the treatment of CML. Its remarkable specificity and efficacy led to consideration of the drug for therapeutic use. There is no doubt that the clinical efficacy and low toxicity of STI571 sets a precedent for the further development of targeted forms of therapy in malignant disease. However, rapid resistance to STI571, high relapse rate of CML and unaffordable medical expense of patients limit its clinical application. So it is crucial to find out new methods to treat CML effectively.CML is probably the most extensively studied human malignancy. The Philadelphia (Ph) chromosome is a constant cellular and genetic feature of CML, which is characterized cytogenetically by a t(9;22)(q34;qll) reciprocal translocation that gives origin to a hybrid bcr-abl gene, encoding a P210(BCR-ABL) fusion protein with elevated tyrosine kinase activity and transforming ability. Th...
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