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LeukemiaEnviron SIGNED

SIGNALING PROPENSITY IN THE MICROENVIRONMENT OF B CELL CHRONIC LYMPHOCYTIC LEUKEMIA

Total Cost €

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EC-Contrib. €

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Partnership

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 LeukemiaEnviron project word cloud

Explore the words cloud of the LeukemiaEnviron project. It provides you a very rough idea of what is the project "LeukemiaEnviron" about.

samples    interactions    mir    re    interleukin    animal    transplantable    function    microenvironmental    implication    nodes    therapeutic    malignancies    cd20    circulate    microenvironments    mechanisms    pro    proliferative    universal    print    normal    constantly    lymphocytic    integrate    proteins    therapies    course    therapeutically    lymph    inhibited    rituximab    signaling    engraftment    regulation    primary    obtain    il4    stable    transferable    unknown    led    finger    receptor    mirnas    responsible    proliferation    figure    first    therapy    nfkb    interaction    influences    bcr    times    see    peripheral    mediated    cd40    disease    vs    activation    biology    immune    node    mouse    hypothesize    relevance    cll    acts    dependency    cells    frequent    niches    stream    signalling    leukemia    pdx    blood    survival    cell    utilized    microenvironment    adults    regulator    model    12    propensity    inhibitors    reveal    complicates    29    chronic    data    malignant    signals   

Project "LeukemiaEnviron" data sheet

The following table provides information about the project.

Coordinator
Masarykova univerzita 

Organization address
address: Zerotinovo namesti 9
city: BRNO STRED
postcode: 60177
website: http://www.muni.cz

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Czech Republic [CZ]
 Total cost 1˙499˙990 €
 EC max contribution 1˙499˙990 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-STG
 Funding Scheme ERC-STG
 Starting year 2019
 Duration (year-month-day) from 2019-06-01   to  2024-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    Masarykova univerzita CZ (BRNO STRED) coordinator 1˙499˙990.00

Map

 Project objective

B cell chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults. CLL cells are characterized by their universal dependency on pro-survival and pro-proliferative signals from immune niches. To achieve this they constantly re-circulate between blood and lymph nodes, which is inhibited by novel microenvironment-targeting therapies such as “BCR inhibitors”. We aim to reveal how the malignant B cells change the propensity of their signalling pathways in response to the different microenvironments such as peripheral blood vs lymph node to obtain the proliferative signals. This is of major relevance for CLL, but also transferable to the biology of some other B cell malignancies and/or normal B cells. We analyzed the “finger print” of microenvironmental interactions in many CLL samples at various times during the disease course or during therapy. The obtained data led us to hypothesize on the mechanisms of regulation of signalling propensity of two pathways that are responsible for proliferation and survival of CLL cells, namely B Cell Receptor (BCR) signalling and signals from T-cells mediated by CD40/IL4. In aim 1 we hypothesize that CD20 is one of the key proteins involved in CLL cell activation, and influences BCR and interleukin signalling (see figure). This has important therapeutic implication since CD20 is used as a therapeutic target for 20 years (rituximab), but its function in CLL/normal B cells is unknown. In aim 2 we hypothesize that miR-29 acts a key regulator of T-cell signalling from CD40 and down-stream NFkB activation (see figure). This represents the first example of miRNAs‘ role in the propensity of T-cell interaction, and could be also utilized therapeutically. In aim 3 we will integrate our data on microenvironmental signaling (aim 12) and develop a first mouse model for PDX that would allow stable engraftment of primary CLL cells. Currently, CLL is non-transplantable to any animal model which complicates studies of its biology.

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The information about "LEUKEMIAENVIRON" are provided by the European Opendata Portal: CORDIS opendata.

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