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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.

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

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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