Title: Synergistic ablation of MLL-Fusion onco-proteins as a novel acute leukaemia therapy
Funder: Action Medical Research

Abstract: Background_x000D_ Leukaemia is the most common cancer affecting children and teenagers, accounting for approximately one in three cancers. Each year in the UK, around 500 new cases are diagnosed in this age group. Research over many years has resulted in vastly improved treatments and most children with leukaemia can now be successfully treated. Unfortunately, certain subtypes of disease have proved more difficult to treat and the outlook for these children is less positive. _x000D_ One type of leukaemia, particularly affecting babies below the age of one, occurs when a gene called MLL fuses to other genes and creates a new, cancer-causing protein called an oncoprotein. Even with the latest cutting-edge therapies, children with this type of leukaemia often do not respond to treatment and new approaches are urgently needed. These researchers plan to target the oncoprotein produced by the fused genes. By inactivating this protein, they may be able to stop the progression of leukaemia and improve the outcome for young patients with this life-threatening disease. _x000D_ _x000D_ The research project_x000D_ The team has recently discovered a potential new treatment consisting of two drugs which together destroy the oncoprotein. These drugs are already established to treat other non-cancer conditions, which means that their pharmacological and safety profiles are well-established. In this project, the researchers will further investigate the safety and efficacy of this drug combination in human cells and a mouse model of leukaemia. If the results are promising, the team hopes to move rapidly into clinical trials. This study will help to determine the most appropriate dose and dose frequency, therefore guiding the design of future trials in patients. Ultimately, the researchers hope that their new, targeted drug combination could save the lives of sick and vulnerable children for whom no effective treatments exist._x000D_ _x000D_ Action Medical Research and LifeArc are jointly funding this research._x000D_ _x000D_ _x000D_

Lay abstract: Background_x000D_ Leukaemia is the most common cancer affecting children and teenagers, accounting for approximately one in three cancers. Each year in the UK, around 500 new cases are diagnosed in this age group. Research over many years has resulted in vastly improved treatments and most children with leukaemia can now be successfully treated. Unfortunately, certain subtypes of disease have proved more difficult to treat and the outlook for these children is less positive. _x000D_ One type of leukaemia, particularly affecting babies below the age of one, occurs when a gene called MLL fuses to other genes and creates a new, cancer-causing protein called an oncoprotein. Even with the latest cutting-edge therapies, children with this type of leukaemia often do not respond to treatment and new approaches are urgently needed. These researchers plan to target the oncoprotein produced by the fused genes. By inactivating this protein, they may be able to stop the progression of leukaemia and improve the outcome for young patients with this life-threatening disease. _x000D_ _x000D_ The research project_x000D_ The team has recently discovered a potential new treatment consisting of two drugs which together destroy the oncoprotein. These drugs are already established to treat other non-cancer conditions, which means that their pharmacological and safety profiles are well-established. In this project, the researchers will further investigate the safety and efficacy of this drug combination in human cells and a mouse model of leukaemia. If the results are promising, the team hopes to move rapidly into clinical trials. This study will help to determine the most appropriate dose and dose frequency, therefore guiding the design of future trials in patients. Ultimately, the researchers hope that their new, targeted drug combination could save the lives of sick and vulnerable children for whom no effective treatments exist._x000D_ _x000D_ Action Medical Research and LifeArc are jointly funding this research._x000D_ _x000D_ _x000D_

Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS