Inhibitor of DUX4-IGH to Erase Acute lymphoblastic Leukaemia

Información del proyecto

IDEAL

Identificador del acuerdo de subvención: 841957

DOI

10.3030/841957

Proyecto cerrado

Fecha de la firma de la CE 11 Abril 2019

Fecha de inicio 1 Febrero 2020

Fecha de finalización 31 Enero 2022

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 171 473,28

Aportación de la UE

€ 171 473,28

Coordinado por

OSPEDALE SAN RAFFAELE SRL
Italy

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

Período documentado: 2020-02-01 hasta 2022-01-31

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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