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LeukemiaEnviron SIGNED

SIGNALING PROPENSITY IN THE MICROENVIRONMENT OF B CELL CHRONIC LYMPHOCYTIC LEUKEMIA

Total Cost €

0

EC-Contrib. €

0

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.

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

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

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 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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