Inhibitor of DUX4-IGH to Erase Acute lymphoblastic Leukaemia

Projektinformationen

IDEAL

ID Finanzhilfevereinbarung: 841957

DOI

10.3030/841957

Projekt abgeschlossen

EK-Unterschriftsdatum 11 April 2019

Startdatum 1 Februar 2020

Enddatum 31 Januar 2022

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 171 473,28

EU-Beitrag

€ 171 473,28

Koordiniert durch

OSPEDALE SAN RAFFAELE SRL
Italy

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

Berichtszeitraum: 2020-02-01 bis 2022-01-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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