H2020Индивидуална стипендия2015–2018

LYMPHOSIGN · Integrated study of the role of B-cell receptor signaling in the development of Follicular Lymphoma

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

Период: 2015-12-01 → 2018-10-31
Финансиране от ЕС: 200 120 €
Участници: 2
Схема: MSCA-IF-GF

Линиите свързват координатора с партньорите.

Накратко на български

Сигналите от рецепторите на B-клетките се анализират, за да се разбере как те стимулират растежа на фоликуларния лимфом. Това е важно, за да се открият нови възможности за терапия при агресивните форми на заболяването, при които сегашните методи често са неефективни.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Integrated study of the role of B-cell receptor signaling in the development of Follicular Lymphoma

Signaling through the B cell receptor (BCR) is central to the development of normal B-lymphocytes. In light of the numerous proliferative and survival pathways activated downstream of the BCR, it comes as no surprise that malignant B cells would co-opt this receptor to promote their own growth and survival. Direct evidence for a role of aberrant BCR signaling in an aggressive lymphoma subtype has only come to light recently showing a constitutive BCR activity that keeps cells alive. B cell receptor (BCR) signaling has emerged as a therapeutic target in B cell lymphomas and are now in clinical trials, but the precise deployment of inhibitors to target oncogenic BCR signaling requires detailed knowledge of the signaling cascades that the BCR triggers in individual tumors. In this project, we aim to better understand the role and function of BCR signaling as a pathogenic mechanism in Germinal center B-cell lymphomas, notably Follicular lymphoma (FL). FL is a relatively indolent disease with actual first-line treatment often providing extended survival over 15 years. Yet, ~20% progress within 2 years of diagnosis or eventually transform into an aggressive and fatal disease with a poor prognosis. Treatment of follicular lymphoma that has transformed into an aggressive lymphoma (tFL) remains an unmet medical need since therapies that are successful in treating other aggressive lymphomas such as diffuse large B cell lymphoma (DLBCL) are often ineffective in tFL. We do not currently have clear strategies for therapeutic development in tFL since we do not understand the molecular mechanisms that sustain the abnormal proliferation and survival of these malignancies. To identify new therapeutic opportunities in tFL, I have devised genetic screens using tFL cell line models derived from patients with this disease to identify genes that control essential cellular processes in these cells. In addition, I have used genetic screens to suggest ways to improve the efficacy of drugs that have shown activity or are approved in other lymphomas but do not work in tFL adequately.

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

Цел на проекта

Signaling through the B cell receptor (BCR) is central to the development and maintenance of B cells. In light of thenumerous proliferative and survival pathways activated downstream of the BCR, it comes as no surprise that malignant Bcells would co-opt this receptor to promote their own growth and survival. However, direct evidence for BCR signaling inhuman lymphoma has only come to light recently. In this proposal, I aim to better understand the role for antigen-dependent vs. antigen-dependent BCR signaling as a pathogenic mechanism in the progression of Follicular lymphoma (FL), a indolent lymphoid malignancy that retain BCR expression during malignant progression. Further investigating the intrinsic role of BCR might lead to the development of new therapeutic approaches based on the inhibition of the BCR pathways. Using an innovative loss-of -function RNA interference genetic screen together with an engineered in vitro system allowing to test FL patients's BCR reactivity and identify putative ligands, we will 1) determine whether BCR signalling in FL relies to""chronic active"" or ""tonic"" signals and 2) identify the nature of antigen(s) recognized by FL's BCR that may sustainsignalling; each signalling pathway offering different opportunities for therapeutic intervention. For this project, I decided to chose the Louis Staudt’s group at the National Cancer Institute (NIH) for the outgoing phase since his group has been looking for years how to target B-cell receptor signaling as a treatment strategy. The unique expertise in the state-of the art functional genomic methodologies acquired during my stay at the NCI will be crucial for setting-up new scientific projects, promote extended collaborations and strongly support my re-establishement in Europe to reach an independent position.""

Оригинален текст от CORDIS (на английски).

Участници

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisКоординаторФранция
United States Department of Health and Human Services · Washington D.C.Съединени щати