Important insights into the process underlying two kinds of leukaemias associated with the CALM-AF10 translocation are reported in a study in the September 2006 issue of Nature Cell Biology.
Chromosomal translocations, where a fragment of a chromosome is broken off and joins another, can generate fusion proteins that are comprised of two gene products. These fusion proteins often 'misregulate' genes that can cause leukaemia. One of the genes most frequently translocated in leukaemia is MLL - mixed lineage leukaemia - and one of its fusion partners is AF10. AF10 has also been shown to fuse with another protein, CALM, in patients with T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia. But it is unclear whether the CALM-AF10 fusion is causal for the disease and there is very little understanding of how this fusion may lead to leukaemia. Yi Zhang and colleagues show that the CALM-AF10 fusion is necessary and sufficient for leukaemic transformation in a mouse model. They found that the fusion leads to atypical expression of the Hoxa5 gene and moreover, that turning on Hoxa5 is necessary for leukaemic transformation induced by the fusion protein. They also identified an enzyme that modifies chromatin as being important for turning up gene expression by the fusion protein.
Whether these findings will result in new and useful therapeutic treatments is unclear at present but understanding the fundamental processes that go awry during cancer development is clearly the first step to developing new treatments.
Yi Zhang (University of North Carolina at Chapel Hill, NC, USA)
Abstract available online.
(C) Nature Cell Biology press release.
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