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Chronic Myeloid Leukemia

The Value of Tyrosine Kinase Inhibition

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American Journal of Cancer

Abstract

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder that results from an acquired genetic change in a single pluripotential hemopoietic stem cell. The molecular hallmark of CML is the BCR-ABL gene rearrangement, which typically is generated by the Philadelphia (Ph) chromosome. The Ph chromosome abnormality arises as a result of a mutated stem cell acquiring a balanced reciprocal translocation involving chromosomes 9 and 22. The chimeric BCR-ABL gene encodes an oncoprotein, termed p210BCR-ABL protein, which has an enhanced and deregulated tyrosine kinase activity. It is generally regarded as the principal molecular cause of the initial indolent stage (chronic phase) of CML and further proof for this notion came from the remarkable activity of the Abl kinase inhibitor, imatinib mesylate (formerly STI 571). Imatinib mesylate targets the autophosphorylation of the Abl kinase specifically and is not only effective in the majority of patients, its also relatively free of major adverse effects. Current experience suggests hematological responses in over 95% of patients in the chronic phase of CML, with about 70% achieving a major cytogenic response. The drug is only able to achieve complete molecular responses in a minority of patients and so may not affect molecular cure. It is noteworthy that patients in the more advanced phases of CML, which involves additional clonal events, also respond to imatinib mesylate but have a high incidence of treatment resistance and relapse.

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Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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Authors and Affiliations

  1. Department of Haematology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK

    Tariq I. Mughal & John M. Goldman

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  1. Tariq I. Mughal
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  2. John M. Goldman
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Correspondence to Tariq I. Mughal.

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Mughal, T.I., Goldman, J.M. Chronic Myeloid Leukemia. Am J Cancer 2, 305–311 (2003). https://doi.org/10.2165/00024669-200302050-00001

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