Article ID Journal Published Year Pages File Type
2100744 Best Practice & Research Clinical Haematology 2009 10 Pages PDF
Abstract

The discovery of the Philadelphia (Ph) chromosome represented the first step towards understanding the molecular basis of haematological malignancies. Subsequent developments including the characterisation of t(9;22)(q34;q11) translocation, the identification of the breakpoint cluster region as well as the demonstration that retrovirally mediated insertion of a human BCR-ABL gene into murine haematopoietic stem cells induced a leukaemia-like picture and the creation of BCR-ABL transgenic mice established the central role of BCR-ABL in chronic myeloid leukaemia (CML) beyond all reasonable doubt. Many years later an important goal was achieved, that is, the use of BCR-ABL as a therapeutic target. However, it is uncertain whether the BCR-ABL fusion gene is really the initiating lesion for the chronic phase of CML. There is an incomplete understanding of the so-called genomic instability that underlies the production of the fusion gene and predisposes the Ph-positive clone to acquire further genetic events leading to advanced-phase disease.

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