H2020Индивидуална стипендия2020–2022

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2020-02-01 → 2022-01-31
Финансиране от ЕС: 171 473 €
Участници: 1
Схема: MSCA-IF-EF-SE

Линиите свързват координатора с партньорите.

Накратко на български

Ново вещество, което блокира активността на генечната мутация DUX4-IGH, се тества върху клетъчни и животински модели на детска лейкемия. Това е важно, защото за пациентите с този специфичен генетичен проблем в момента няма подходящо лечение.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Inhibitor of DUX4-IGH to Erase Acute lymphoblastic Leukaemia

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.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

OSPEDALE SAN RAFFAELE SRL · MilanoКоординаторИталия