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Leukaemia Research

Positional cloning : from chromosomes to chimaeric genes in human leukaemia

The molecular dissection of structural chromosome alterations found in cancer cells has identified more than 100 cancer-related genes. Aside from their diagnostic and prognostic value, this genetic information is providing new information that is critical to our current understanding of the molecular pathways of cancer development and progression. A better understanding of these pathways is a necessary precedent to the design of more effective treatments.

 

 

 

Structural chromosome rearrangements contribute to malignant transformation by one of two main mechanisms - either by the deregulation of a cellular gene, or by creating a transforming fusion gene. In the latter case, the genes at the breakpoint junctions of chromosome translocation are often transcription factors, and normally involved in developmental processes of cell differentiation. We are studying a novel t(5;10)(q22;q24) associated with acute lymphoblastic leukaemia (ALL), and our research to date has identified a single large-insert genomic clone that contains the 10q24 breakpoint. Our current investigations aim to identify the site of breakage within this clone, and to identify and characterise genes that span or map close to its vicinity.