Inhibitor of DUX4-IGH to Erase Acute lymphoblastic Leukaemia

Project Information

IDEAL

Grant agreement ID: 841957

DOI

10.3030/841957

Project closed

EC signature date 11 April 2019

Start date 1 February 2020

End date 31 January 2022

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 171 473,28

EU contribution

€ 171 473,28

Coordinated by

OSPEDALE SAN RAFFAELE SRL
Italy

Periodic Reporting for period 1 - IDEAL (Inhibitor of DUX4-IGH to Erase Acute lymphoblastic Leukaemia)

Reporting period: 2020-02-01 to 2022-01-31

Summary of the context and overall objectives of the project

The second most important cause of death and morbidity in Europe is cancer and B-cell acute lymphoblastic leukaemia (BALL) is the most common paediatric cancer and cause of cancer-related death before 20 years. In up to 7-10% of cases, this disease is caused by genetic rearrangements giving rise to the DUX4-IGH fusion. A specific treatment for these patients is currently unavailable, therefore this project aims to investigate the possibility to develop new therapeutic strategies for the treatment of B-ALL with DUX4-IGH rearrangements. In particular we aim to test a novel inhibitor of DUX4-IGH transcriptional activity and its pathological consequences, using both cellular and animal model of the disease.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the reporting period, I used an approach combining in vitro and in vivo analyses to test the potential antileukemic activity of a new inhibitor of DUX4-IGH+ve leukemia.
In particular I exploited both a cellular model and a humanized animal model to test the efficacy of this inhibitor.
I found that delivery of the inhibitor is associated to inhibition of DUX4-IGH leukemia cell growth and inhibition of DUX4-IGH biological functions (such us modulation of target genes and proteins).
I tested the specificity of the inhibitor exploiting different cell lines and approaches.
I demonstrated that the expression of this inhibitor is detrimental to DUX4-IGH leukemia cells expansion in immunocompromised animals.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The results of the projects overall support the antileukemic activity of the DUX4-IGH inhibitor.
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.

IDEAL: Inhibitor of DUX4-IGH to Erase Acute lymphoblastic Leukaemia