H2020Индивидуална стипендия2016–2018

CIRCLE · Investigation of the role of CYLD in Chronic Lymphocytic Leukaemia

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

Период: 2016-04-15 → 2018-04-14
Финансиране от ЕС: 180 277 €
Участници: 1
Схема: MSCA-IF-EF-ST

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Накратко на български

Ролята на протеина CYLD при хроничната лимфоцитна левкемия се анализира чрез компютърни и живи модели. Разбирането на този механизъм може да помогне за откриването на нови мишени за терапевтично лечение на заболяването.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Investigation of the role of CYLD in Chronic Lymphocytic Leukaemia

Chronic Lymphocytic Leukemia (CLL) is the most common type of Leukemia in the western world, affecting 6 every 100,000 individuals every year and is characterized by the accumulation of CD19+/CD5+ B cells in the peripheral blood and lymphoid organs of the patients. It is considered a disease of the elder male, since the median age at diagnosis is 72 years and the proportion of male:female patients is 2:1. CLL has a median survival of 10 years but the course can be very heterogeneous. In some more aggressive cases, patients succumb to the disease after 2-3 years, whereas in indolent cases the lifespan of the patient may not be affected. The cause of the disease is unknown, even though disease susceptibility and prognosis has been associated with several genetic factors. CYLD is a functional ubiquitinase, involved in the removal of ubiquitin chains that were attached to proteins to change their structure and enable interaction with other proteins in signaling pathways, rather than proteasomal degradation. CYLD was discovered in patients affected by a benign form of skin tumor but it was later revealed to have a tumor suppressor action in different types of solid and hematological tumors. Despite introduction of novel therapeutic agents, CLL remains at large incurable generating an important societal burden, both in terms of caring and well-being of the general population and of treatment costs. With the EU population growing constantly older, such diseases are expected to pose an ever-growing risk, and an EU strategic agenda has been implemented to address it. The overall objective of the project was to elucidate the role of CYLD in CLL, using in vivo and in silico models. Understanding the role of CYLD in CLL could reveal novel targets for therapeutic interventions or markers for disease prognosis.

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

Цел на проекта

This project will investigate the role of CYLD in Chronic Lymphocytic Leukaemia (CLL). CYLD is a deubiquinating enzyme acting as a tumour suppressor in numerous tumours. CLL is characterized by the accumulation of B-lymphocytes. It affects mostly the elder and has a high incidence rate in Europe. Recent data from CYLD knockout murine models indicate a link between CYLD and CLL, however the approach used for generation of these mice led to contrasting results.At the core of this interdisciplinary project is the generation of two transgenic murine with: i) targeted CYLD inactivation in B-lymphocytes, ii) targeted inactivation combined with a murine model of CLL. Targeted inactivation will be achieved using the Cre-Lox system, by crossing already available progenitor mice. The mice will be extensively characterized with an emphasis on B-lymphocytes development and pathophysiology. RNA-seq will be used to find differentially expressed genes in B-lymphocytes. Computational biology approaches will then be applied to identify the affected pathways, which will be evaluated against publicly available human CLL data, seeking wider consensus.CYLD targeted inactivation allows for the first time evaluation of CYLD's role in B-lymphocytes development and CLL ruling out the effect CYLD inactivation in other cells may have. This project will enable better understanding of the role of CYLD in B-lymphocytes biology and could unravel novel biomarkers and therapeutic targets. At the same time the applicant will train-through-research, master novel techniques and develop soft skills valuable for his future career.This project combines the applicant’s expertise in the generation and characterization of murine models with targeted CYLD inactivation with the host's long track record in B-lymphocytes and CLL.It falls well within the EU’s research agenda, which emphasizes interdisciplinary research leading to recognition of common disease mechanisms and identification of novel biomarkers.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITA VITA-SALUTE SAN RAFFAELE · MilanoКоординаторИталия