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Chronic myeloid eukemia is a clonal myeloproliferative disorder caused by a neoplastic transformation of the pluripotent hematopoietic stem cell.Many features of the disease make it as a good model for studying the development of cancer in humans.In the first stages of CML, most people dont have symptoms and the disease progresses slowly.After a chronic phase of variable duration (0.5 to 15 yrs), the disease almost invariably undergoes transformation.Without curative interventions, CML progresses into a fatal blast crisis, which resembles acute leukemia, but is incurable by chemotherapy.In some individuals, acute phase is preceded by an intervening, "subacute" phase associated with marked changes in the bone marrow morphology.The biphasic or triphasic clinical course of the disease exemplifies the multi-step process of tumor progression from the indolent "preneoplastic" phase to a more aggressive terminal blast crisis.The progression is associated with marked changes in proliferation, differentiation, apoptosis, and adhesion serving CML as a paradigm of studying the process of oncogenesis in humans.Another feature of CML that makes it as a good model of oncogenesis is the presence of an unique genetic anomaly, the Philadelphia (Ph) chromosome and the BCR-ABL chimeric gene.While the BCR-ABL fusion is believed to be the primary cause of the CP of CML, current research indicates that disease progression requires further genomic changes serving CML as a model of studying the development of new mutations.The seemingly stereotypical march of CML progression involves changes in proliferation, differentiation, genetic instability and DNA repair, telomere shortening and the loss of tumor-suppressor functions.Those features are relevant for most human cancers, and thus CML may serve as a unique model of cancer evolution and progression.Throughout its history, CML has set precedents in cancer, ranging from the identification of the first karyotypic anomaly in cancer to the development of specifically designed targeted therapy for the disease.In addition, the dramatic efficacy of tyrosine konase inhibitors in CML patients offers proof that molecular targeting works in treating cancer and may serve as a pattern for how future cancer research may be successfully done.At present, the model of oncogenesis as a result of the Ph transloeation is one of the clearest models of translocation-mediated gene activation in human cancer and is among the best examples of a malignancy that can be studied in precise molecular terms.