Some pioneer studies have shown the potential of using gene-editing technologies to model human malignancies. We propose to use such technologies to generate a cellular model for a deadly form of infant leukaemia.
Excellent progress has been made in the cure of childhood leukaemia in the past 20 years, achieving complete remission in more than 90% of acute lymphoid leukaemia sufferers. However, a proportion of very young patients still die of acute myeloid leukaemia. The cancer cells of these children harbour a specific genetic rearrangement between chromosomes 7 and 12, known as t(7;12). This chromosomal abnormality disrupts the function of two genes: ETV6 (normally involved in the production of blood cells), and HLXB9 (involved in the normal development of the embryo).
The exact mechanism that leads to this deadly form of leukaemia due to the interaction of these two genes is still unclear. Due to the short life span of these young patients, availability of bone marrow samples is limited impacting on the number and type of studies possible. An ideal study tool would be an in-vitro cellular model that contains the same genetic characteristics of the leukaemia cells found in the patients. Some pioneer studies have shown the potential of using DNA modification methods (gene-editing technologies) to model human malignancies. We propose to use such technologies to generate a cellular model for the t(7;12) leukaemia. This will help us understand the biology of the disease and identify molecular targets leading to a possible new treatment.
The potential impact of this research project is far reaching. The generation of a cellular model for the t(7;12) chromosome rearrangement will enable us to make the critical breakthrough in identifying the biological mechanisms that initiate this specific type of infant leukaemia. The natural next step would be the development of new and less harmful drugs and therapies to cure children from this deadly disease. This project has the real potential to improve the survival rate of children suffering from the disease worldwide. Furthermore, the findings emanating from this research project can be extrapolated and applied to the understanding and treatment of other cancers.
Meet the Principal Investigator(s) for the project
Dr Sabrina Tosi - Dr Sabrina Tosi graduated in Biological Sciences at the University of Milan (Italy) in 1989 and then attained her post-graduate degree in Human Cytogenetics at the University of Pavia (Italy) in 1992. Between 1989 and 1993 she was a research scientist at the Department of Paediatric Haematology, University of Milan, Ospedale San Gerardo, Monza (Italy). During this time she worked also as a visiting research scientist at Oncogenetic Laboratory, Children's Hospital, University of Giessen (Germany) for approximately a year. In 1994, Dr Tosi transferred to the University of Oxford to work as a research scientist, she then enrolled and completed her DPhil studies in 1999. She continued to work at the University of Oxford until July 2005, when she was appointed as Lecturer in Biosciences at 小湿妹视频 London.
Related Research Group(s)
Inflammation Research and Translational Medicine - Driving scientific innovation and discovery for diagnosis, treatment, and management of cardiovascular disease, inflammatory and immune disorders, microbial resistance, and cancer.
Genome Engineering and Maintenance - Diverse research network focused on molecular, cellular, organismal and computational aspects of genome biology.
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Project last modified 13/11/2023