Dr Marcela Braga Mansur, a Leukaemia UK John Goldman Fellow, aims to identify which cell type is first affected by the MLL-AF4 mutation that causes leukaemia and if there are differences in the cells affected according to age when comparing children and adults.

The challenge

Leukaemia is often caused by mutations in specific genes, and one such mutation is called MLL-AF4. MLL-AF4+ leukaemias can be found in babies, children, and adults, though the disease is different in each of these age groups in terms of outcomes with children and adults doing better than babies.

Unfortunately, leukaemias which carry this MLL-AF4 mutation are often very aggressive and resistant to drugs that usually work for other types of leukaemia. So, there is a need to find new treatments for MLL-AF4 leukaemias, to then give everyone the best chance of survival.

The science behind the research

The production of blood in our bone marrow is organised like a hierarchy. At the top are the haematopoietic stem cells, which can produce any type of blood cell and renew themselves. Below them are progenitor cells, which can produce only certain type of cells. And at the bottom are the specialised cells (red blood cells, B cells, T cells, etc) which do all the work, but can’t produce other types of cells.

When it comes to MLL-AF4 leukaemia, one of the things we don’t know is in which stem or progenitor cell type the MLL-AF4 mutation first happens– the so-called ‘cell-of-origin’. It’s likely that this cell-of-origin is different for each of the age groups affected, and this might explain some of the differences in the disease between children and adults.

During her John Goldman Fellowship, Dr Marcela Braga Mansur will use cutting-edge techniques to study samples donated by babies, children, and adults with MLL-AF4 leukaemia. By looking at the genetics of individual or so called single-cells, Marcela hopes to identify the cell-of-origin for the different types of MLL-AF4 leukaemia, and then try to understand what makes the disease different in these age groups.

What difference will this research make?

Marcela’s project will answer a fundamental question about which cell type is originally affected by the MLL-AF4 mutation in leukaemia. This will provide clues for how the disease becomes resistant to treatment, and shed light on how the disease may differ between babies, children, and adults.

In the long-term, Marcela’s work could present new opportunities for treatments to stop people dying from this aggressive blood cancer and offer new venues to investigate the disease in different age groups.