Inhibitor of DUX4-IGH to Erase Acute lymphoblastic Leukaemia

Informations projet

IDEAL

N° de convention de subvention: 841957

DOI

10.3030/841957

Projet clôturé

Date de signature de la CE 11 Avril 2019

Date de début 1 Février 2020

Date de fin 31 Janvier 2022

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 171 473,28

Contribution de l’UE

€ 171 473,28

Coordonné par

OSPEDALE SAN RAFFAELE SRL
Italy

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

Période du rapport: 2020-02-01 au 2022-01-31

Résumé du contexte et des objectifs généraux du projet

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.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

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.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

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