Abstract:

Chronic Myeloid Leukaemia (CML) is a clonal disorder of a pluripotent stem cell characterized by the Philadelphia (Ph) chromosome. The Ph is a shortened chromosome 22 resulting from a reciprocal translocation between the BCR gene on chromosome 22 and the ABL gene on chromosome 9 (Mondal et al., 2006). The resulting overactive ABL tyrosine kinase appears to be responsible for uncontrolled myeloid cell proliferation (Hughes et al., 2006). Imatinib, also called Gliveec, is the first and most commonly used tyrosine kinase inhibitor (TKI) that inhibits by binding through ATP (adenosine triphosphate) onto the BCR-ABL fusion protein of which when absent the kinase leads to uncontrolled cell proliferation. The level of BCR-ABL mRNA can be used as a sensitive marker for disease progression (Hoffbrand et al., 2001). In approximately 5% of CML cases, patients present with a variant Ph chromosome in which the Ph chromosome is derived through rearrangements other than the classic t(9;22) (Hughes, et al., 2006).

The aim of this study is to assess the response to therapy between classic chronic myeloid leukaemia patients and variant translocation chronic myeloid leukaemia patients. Methods for monitoring treatment response include conventional cytogenetic analysis, Fluorescence in situ hybridization (FISH) and Quantitative PCR (polymerase chain reaction). BCR-ABL transcript levels quantified by PCR will be used to assess the response of therapy, which in turn influences the choice of clinical management. The response in therapy will be monitored in patients with variant Ph translocations compared to patients with classical Ph translocation who have or have not responded to treatment.

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