New research identifies drivers of aggressive infant leukaemia

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Acute lymphoblastic leukaemia is one of the most common cancers in children. The majority of patients respond well to existing treatments, however patients with a particular form of the disease -  t(4;11) MLL-AF4 acute leukaemia - have a very poor prognosis.

Despite this poor prognosis, scientists have little information about the molecular mechanisms responsible for the disease progression, which hinders the development of new treatments.

New research from the Ottersbach Lab at the Centre for Regenerative Medicine has identified two microRNAs (RNA molecules that control gene expression) as key players in MLL-AF4 leukaemia.

Using a new mouse model, their research shows that these microRNAs (miR-130b and miR-128a) drive the transition of the disease from a pre-leukemic stage to an acute leukaemia.

The team also identified two downstream targets of these microRNAs that act as tumour suppressor genes. These provide a focus for future research into treatments.

Scientists have previously found it difficult to model the disease because of its prenatal origin. However, this new model accurately represents many of the features of the disease in humans.

This new model provides us with a unique opportunity to identify co-drivers that act alongside the initiating MLL-AF4 mutation and to uncover how one mutation can cause different types of leukaemia. It also gives us the chance to tackle very serious complications associated with infant blood cancer, such as central nervous system infiltration, which is replicated in our model.

Professor Katrin Ottersbach, Group Leader, Centre for Regenerative Medicine

The research provides a platform for scientists to identify the drivers of an aggressive infant leukaemia, allowing them to explore disease progression. The team hope this may lead to the development of new treatments in the future.

The study has been published in Blood (Malouf et al., PMID: 34111240) and was funded by the Kay Kendall Leukaemia Fund and Cancer Research UK.

Blood article

Katrin Ottersbach Research Group