Finding new genes
Discovering new genes involved in leukaemia
Dr Sheryl Gough receives funding support from the LBF to research leukaemia-related genes.
Gough, of the Cancer Genetics Research Group (CGRG) at the Christchurch School of Medicine and Health Sciences, is continuing research she began for her PhD thesis.
It involves determining what genes are disrupted at the sites (called breakpoint sites) where chromosome 5 and chromosome 10 have broken and incorrectly rejoined to each other, in what is referred to as a t(5;10) chromosome translocation. This genetic abnormality was found to be specific to the leukaemic cells of an acute lymphoblastic leukaemia (ALL) patient.
The leukaemia associated t(5;10) chromosome translocation has not been described before and contributes to the international knowledge of chromosome translocations in the leukaemias.
Gough has continued with the study to determine more about a new, potentially leukaemia-related gene that she has found to be broken in half on chromosome 10. Current studies focus on describing the structure and activity of this gene and its potential role, if any, in leukaemia. Gough’s research also focuses on the mapping of the chromosome 5 breakpoint site to see what genes on 5 might be joined to the new gene at the chromosome 10 site, and the screening of additional ALL patients for this same leukaemia-related abnormality.
The t(5;10) research, original to New Zealand, was presented at the American Association of Cancer Research Annual Meeting in Los Angeles, and to the University of California, Los Angeles (UCLA) Cancer Centre.
This work is important because patients with specific genetic abnormalities in their leukaemic cells have been shown to respond better to particular treatments, and currently many patients have no such defined genetic abnormality so crucial to guiding clinical diagnosis, treatment selection, and treatment monitoring. Importantly, in recent years these genetic abnormalities have also lead to the development of less toxic drugs targeted against specific gene products, such as imatinib mesylate (Glivec) in chronic myeloid leukaemia. Identifying more of the genes involved in leukaemia is necessary for the development of these types of drugs and for the understanding of the biology of the various leukaemias.
Gough recognises the significant LBF contribution which has helped the ongoing viability of this project. Funds have met the lab costs of the last two years and supported presentation of the work at previous international conferences in the United States. She notes that she originally started in the CGRG as an LBF-supported summer student working on a similar project on the genetics of CML and says “it is now nice to hand on some of that knowledge to another LBF-supported summer student”.
The t(5;10) study was prompted several years ago with the observation of the novel chromosome translocation by Associate Professor Christine Morris in her role as a consultant to the Cytogenetics Unit at the Canterbury Health Laboratories. Morris is Director of the CGRG team, comprised of nine scientists and a haematologist from the Canterbury Health Laboratories, with four major leukaemia projects in progress and others in development.
