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Autonomous CLL-BCRs SIGNED

Role of autonomous B cell receptor signalling and external antigen in the pathogenesis of chronic lymphocytic leukaemia (CLL)

Total Cost €

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EC-Contrib. €

0

Partnership

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 Autonomous CLL-BCRs project word cloud

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Project "Autonomous CLL-BCRs" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAET ULM 

Organization address
address: HELMHOLTZSTRASSE 16
city: ULM
postcode: 89081
website: www.uni-ulm.de

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 Germany [DE]
 Total cost 2˙256˙250 €
 EC max contribution 2˙256˙250 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-11-01   to  2021-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAET ULM DE (ULM) coordinator 2˙256˙250.00

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 Project objective

The proposed project aims at investigating the molecular mechanisms that activate B cell antigen receptor (BCR) signalling in chronic lymphocytic leukaemia (CLL). While it is widely accepted that the unbroken BCR expression in CLL cells is indicative for a key role in disease development, the mechanisms that induce BCR activation and survival of malignant cells are still elusive. Using a unique reconstitution system, we have recently shown that CLL-derived BCRs possess the exceptional capacity for cell-autonomous signalling independent of external antigen. Crystallographic analyses confirmed our model that CLL-BCRs bind to intrinsic motifs in nearby BCRs on the very same cell. In addition to the BCR, several pathogenic factors influence the biological behaviour of CLL cells, but the functional hierarchy and the effect on BCR signalling are insufficiently understood. Here, we aim at investigating the structural cause of autonomous signalling as well as the characterization of important signalling pathways and their mechanistic action in CLL pathogenesis. By combining crystallography with the measurement of autonomous signalling of wild type and mutated receptors in our unique reconstitution system, we will generate a structure-function relationship for CLL-BCRs. By generating new animal models and by employing classical as well as cutting-edge approaches of biochemistry and molecular/cellular immunology, we will comprehensively characterize the signalling pathways that are activated by autonomous signalling and might be important for CLL pathogenesis. These systematic efforts are necessary to understand how various biological mechanisms operate and ultimately activate downstream pathways that result in a lymphoproliferative disease. In addition, a cohesive model of CLL pathogenesis, which elucidates the hierarchical order of pathogenic factors and their interaction with BCR signalling, may well lead to novel disease-specific preventive or therapeutic intervention.

 Publications

year authors and title journal last update
List of publications.
2019 Joseena Iype, Moumita Datta, Ahmad Khadour, Rudolf Übelhart, Antonella Nicolò, Tim Rollenske, Marcus Dühren-von Minden, Hedda Wardemann, Palash C. Maity, Hassan Jumaa
Differences in Self-Recognition between Secreted Antibody and Membrane-Bound B Cell Antigen Receptor
published pages: 1417-1427, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1800690
The Journal of Immunology 202/5 2019-06-13
2018 Palash C. Maity, Moumita Datta, Antonella Nicolò, Hassan Jumaa
Isotype Specific Assembly of B Cell Antigen Receptors and Synergism With Chemokine Receptor CXCR4
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.02988
Frontiers in Immunology 9 2019-06-06
2018 Ameera Alsadeq, Lennart Lenk, Anila Vadakumchery, Antony Cousins, Christian Vokuhl, Ahmad Khadour, Fotini Vogiatzi, Felix Seyfried, Lueder-Hinrich Meyer, Gunnar Cario, Elias Hobeika, Klaus-Michael Debatin, Christina Halsey, Martin Schrappe, Denis M. Schewe, Hassan Jumaa
IL7R is associated with CNS infiltration and relapse in pediatric B-cell precursor acute lymphoblastic leukemia
published pages: 1614-1617, ISSN: 0006-4971, DOI: 10.1182/blood-2018-04-844209
Blood 132/15 2019-06-06
2018 Gang Xiao, Lai N. Chan, Lars Klemm, Daniel Braas, Zhengshan Chen, Huimin Geng, Qiuyi Chen Zhang, Ali Aghajanirefah, Kadriye Nehir Cosgun, Teresa Sadras, Jaewoong Lee, Tamara Mirzapoiazova, Ravi Salgia, Thomas Ernst, Andreas Hochhaus, Hassan Jumaa, Xiaoyan Jiang, David M. Weinstock, Thomas G. Graeber, Markus Müschen
B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies
published pages: 470-484.e18, ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.02.048
Cell 173/2 2019-06-06
2017 Claudia Minici, Maria Gounari, Rudolf Übelhart, Lydia Scarfò, Marcus Dühren-von Minden, Dunja Schneider, Alpaslan Tasdogan, Alabbas Alkhatib, Andreas Agathangelidis, Stavroula Ntoufa, Nicholas Chiorazzi, Hassan Jumaa, Kostas Stamatopoulos, Paolo Ghia, Massimo Degano
Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukaemia
published pages: 15746, ISSN: 2041-1723, DOI: 10.1038/ncomms15746
Nature Communications 8 2019-06-06
2018 Corinna S. Setz, Eva Hug, Ahmad Khadour, Hend Abdelrasoul, Mayas Bilal, Elias Hobeika, Hassan Jumaa
PI3K-Mediated Blimp-1 Activation Controls B Cell Selection and Homeostasis
published pages: 391-405, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.06.035
Cell Reports 24/2 2019-06-06
2019 Joseena Iype, Moumita Datta, Ahmad Khadour, Rudolf Übelhart, Antonella Nicolò, Tim Rollenske, Marcus Dühren-von Minden, Hedda Wardemann, Palash C. Maity, Hassan Jumaa
Differences in Self-Recognition between Secreted Antibody and Membrane-Bound B Cell Antigen Receptor
published pages: 1417-1427, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1800690
The Journal of Immunology 202/5 2019-06-06
2018 Katharina Imkeller, Stephen W. Scally, Alexandre Bosch, Gemma Pidelaserra Martí, Giulia Costa, Gianna Triller, Rajagopal Murugan, Valerio Renna, Hassan Jumaa, Peter G. Kremsner, B. Kim Lee Sim, Stephen L. Hoffman, Benjamin Mordmüller, Elena A. Levashina, Jean-Philippe Julien, Hedda Wardemann
Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope
published pages: 1358-1362, ISSN: 0036-8075, DOI: 10.1126/science.aar5304
Science 360/6395 2019-06-06
2019 Corinna S Setz, Ahmad Khadour, Valerio Renna, Joseena Iype, Eva Gentner, Xiaocui He, Moumita Datta, Marc Young, Lars Nitschke, Jürgen Wienands, Palash C Maity, Michael Reth, Hassan Jumaa
Pten controls B‐cell responsiveness and germinal center reaction by regulating the expression of IgD BCR
published pages: e100249, ISSN: 0261-4189, DOI: 10.15252/embj.2018100249
The EMBO Journal 2019-06-06

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