Acute leukaemia in infants and adult leukaemia caused by cancer treatment has poor outcomes. New treatments are urgently needed for these patients. 

Recurrent translocations (unusual rearrangement of chromosomes) are a mark of leukaemia. These translocations generate fusion oncoproteins (proteins created through the joining of two or more genes that originally coded for separate proteins), that target developmental programs critical for cancerous growth of these leukaemic cells. Meaning that in most cases, we understand the molecular (smallest units that make up a cell) drivers, these so called fusion oncoproteins, of the disease and consequently know what to target. However, in most cases we are unable to do so because the target is “undruggable,” simply not agreeable to intervention with our current treatment protocols.

In my laboratory, we are focused on developing therapeutic approaches that target fusion protein for destruction. We focus on approved small molecules to promote destruction of fusion proteins. To achieve this, we developed a screening platform that screens drugs for their ability to induce targeted destruction of oncoproteins. We focused our attention on acute leukaemia in infants and adult leukaemia caused by cancer treatment, as these have a poor outcome. Our screening platform identified drugs that destroys the mutated protein responsible for this leukaemia. This exciting breakthrough could be a game changer in the treatment of this disease. Indeed, pre-clinical studies showed a significant reduction on the disease levels.

What could this mean for people affected by leukaemia? 

We recently discovered a potential new treatment that destroys this fusion protein. Fusion proteins are the driving oncoproteins in many leukaemias, their inactivation, when possible, has resulted in good long-term outcomes, as shown in patients with Acute Promyelocytic Leukaemia or patients suffering from Chronic Myeloid Leukaemia. We have now identified drugs that destroys the fusion oncoprotein in infant leukaemia. This project funded by Leuka will lead to clinical trials that have the potential to completely change the life of these patients.

The funding of Leukaemia UK allows us to bridge the step from laboratory to clinical trials. We hope that this discovery will be a game changer for these vulnerable babies suffering from this disease.

Dr Jasper de Boer, UCL Institute of Child Health

Official title of project: Therapeutic targeting of MLL-fusion degradation in acute myeloid leukaemia