CORDIS - EU research results

Inhibitor of DUX4-IGH to Erase Acute lymphoblastic Leukaemia

Project description

Closing in on a leukaemia inhibitor

Cancer is the second leading cause of death globally. The most common paediatric cancer is a particularly aggressive type of blood cancer, B-cell acute lymphoblastic leukaemia (B-ALL). A genetic alteration is responsible for some of the cases and, recently, researchers discovered a molecule that may stop the rearranged sequence from activating its target genes. However, the question remains whether this inhibitor will prevent the transformation leading to the development of leukaemia. The IDEAL project is going to find out, testing the inhibitor in both cellular and animal models. These preclinical tests are an important step on the path to improving treatment and patient outcomes.


The second most important cause of death and morbidity in Europe is cancer and B-cell acute lymphoblastic leukaemia (B-ALL) is the most common paediatric cancer and cause of cancer-related death before 20 years. In up to 7% of cases, the disease is caused by rearrangements of the genetic regulator DUX4 to the IGH locus, giving rise to the DUX4-IGH fusion. While ectopic expression of DUX4 induces cell death, DUX4-IGH drives transformation. Even though the two proteins share the same DNA binding domain (dbd), DUX4 and DUX4-IGH drive the transcription of non-overlapping target genes. Through proteomics, my lab identified a specific DUX4-IGH inhibitor, which directly binds to DUX4-IGH dbd blocking the activation of target genes. Based on this evidence, the goal of IDEAL is to test the antileukemic activity of the inhibitor in pre-clinical settings.
Using cellular models, I will test the ability of the inhibitor to block transformation driven by DUX4-IGH. I expect to see a significant inhibition of DUX4-IGH driven transformation in the presence of its inhibitor, associated with reduced proliferation, clonogenic and self-renewal potential. To test the efficacy of DUX4-IGH inhibition in leukemia development, I will employ animal models (murine bone marrow transplantation assays and patient derived xenografts of DUX4-IGH B-ALL) and assess disease latency in the presence or absence of the inhibitor. I predict that the inhibitor will block or significantly delay DUX4-IGH B-ALL.
Pre-clinical validation of the DUX4-IGH inhibitor will help defining effective therapeutic strategies for DUX4-IGH B-ALL patients, improving clinical outcome and lowering treatment toxicity, thus overall promoting Europe's healthcare.
Through IDEAL I will expand my expertise in leukaemia research and I will acquire project management and leadership abilities that will foster my personal and professional development as an independent scientist.


Net EU contribution
€ 171 473,28
20132 Milano

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Nord-Ovest Lombardia Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Total cost
€ 171 473,28