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Modelling the t(7;12) Infant Leukaemia using Gene Editing Technology

Funding body

Kidscan Children's cancer research

Investigator(s)

Principal investigator: Sabrina Tosi
Co-investigator: Arturo Sala
Co-investigator: Giorgia Santilli
 

Project description

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. This will help us understand the biology of the disease and identify molecular targets leading to possible new treatment.

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 possible new treatment.

Impact statement

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.