BCRES-CLL · B cell receptor engagement and signalling in chronic lymphocytic leukemia: identify the structural and functional requirements for disease development and progression.
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2022-03-31 → 2024-03-30
- Финансиране от ЕС
- 183 473 €
- Участници
- 1
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Белите кръвни клетки при хроничната лимфоцитна левкемия се изследват, за да се разбере как протеинът BCR стимулира неконтролирания им растеж. Познаването на тези механизми и свързаните с тях гени помага за разработването на по-ефективни терапии с по-малко странични ефекти.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
B cell receptor engagement and signalling in chronic lymphocytic leukemia: identify the structural and functional requirements for disease development and progression.
B-cell chronic lymphocytic leukemia (CLL) is a common type of cancer where a specific type of white blood cell (called B cells or B lymphocytes) grows out of control. It's characterized by the presence, on the leukemic cells, of a protein called CD5. The disease is quite challenging to treat, and we still don't fully understand why it develops or how it progresses. This project aimed to uncover part of the mysteries behind the role of a key protein called the B-cell receptor (BCR) in CLL. A better understanding of how the BCR works in this disease could lead to new treatments. Current therapies offer some relief and extend the lives of patients with CLL, but they also come with side effects, unintended effects, and the problem of tumors becoming resistant to treatment. Moreover, since these treatments don't provide a complete cure, they also put a heavy burden on healthcare systems worldwide. Thus, a better understanding of the cellular mechanisms involved in CLL will allows for the development of novel, more potent therapies, directly benefit patients by reducing side effects and prolonging remission periods, and indirectly by easing the financial strain on healthcare systems. The goal of the project included the identification of several features implicated with the key protein of the CLL leukemic cells, the BCR, the link of these feature with the various ways a CLL cell can uncontrollably grow in response to agents present in our bodies, and the identification of genes involved in this process that could be potentially exploited for the development of novel therapies. Concomitantly, to carry this goal out, the project aimed to develop a machine learning algorithm that could help to identify non-obvious relationships among the different clinical and biological features evaluated.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
B-cell chronic lymphocytic leukemia (CLL), the most prevalent leukemia among adult Caucasians, is a disease characterized by the clonal expansion of B lymphocytes expressing CD5. The B-cell receptor (BCR) plays a critical role in CLL development and progression as indicated by the efficacy of drugs blocking BCR signaling. However, the mechanism(s) underneath BCR responsiveness are not well-defined and CLL remains incurable. In the classical view, an interaction between BCR and extrinsic antigen is responsible for such signalling. The discovery that CLL BCRs can self-associate and signal in the absence of extrinsic antigens (intrinsic binding) highlighted a novel mechanism for BCR engagement and signalling. Growing amount of evidences suggest that both extrinsic and intrinsic engagement are required for leukemia development and progression. Herein, we aim to better define the selectiveness of the two BCR engagement mechanisms and their association with specific biological and clinical characteristics. To better define such elusive associations, machine learning algorithms will be developed and used to define the specific links among the biological data. Specifically, we will i) assess BCR engagement features associated with CLL clinical aggressiveness and responsiveness to stimuli; ii) identify normal B cells expressing CLL-like BCRs and evaluate their engagement features and similarity with CLL B cells; iii) identify genes and genetic pathways distinctly associated with either mechanism of BCR engagement and/or CLL aggressiveness.The successful outcome of this proposal would generate biologically and clinically relevant information for prevention, prognosis and therapy of CLL.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITA DEGLI STUDI DI GENOVA · GENOVAКоординаторИталия
Връзки
Данни: CORDIS, © Европейски съюз