Abstract
The one universal characteristic of leukaemogenesis is the acquisition of specific chromosomal abnormalities with proven causality to oncogenes. Since the molecular characterization of the translocation involving the c-MYC gene in Burkitts lymphoma, our understanding of the pathways by which genetic translocations in haematologic malignancy lead to oncogenesis has increased dramatically. Molecular studies of the genes involved in these somatic rearrangements and the analysis of their function has elucidated their role in the initiation of tumorigenesis and the sustained cellular growth characteristic of the transformed cell. In global terms, the progression to the malignant state that accompanies translocations appears to proceed not through a single event but multiple steps including but not limited to : (1) the altered expression of DNA regulatory molecules that transcriptionally activate photo-oncogenes requisite for transformation; (2) the deregulation of gene products that control terminal differentiation; (3) the activation of growth factors or their receptors whose overexpression sustains unlimited cell growth; and/or (4) the activation of factors that prevent programmed cell death or apoptosis. Moreover, several preleukemic diseases show evidence of only one predisposing event, which by itself is insufficient to produce the complete immortalization of a cell. This has significant implications for the development of novel strategies for therapeutic intervention which may lead to new “fourth” generation modalities of treatment to reverse these changes through the use of recombinant biologics or gene therapy.
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Goodenow, R.S. (1995). Translocation in Cancer: Mechanism of Oncogenic Conversion and Implications for Therapy. In: Sibinga, C.T.S., Das, P.C., Briët, E. (eds) Hereditary Diseases and Blood Transfusion. Developments in Hematology and Immunology, vol 30. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2017-7_11
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DOI: https://doi.org/10.1007/978-1-4615-2017-7_11
Publisher Name: Springer, Boston, MA
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