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LeukaemiaTargeted SIGNED

Selecting genetic lesions with essential function for patients' leukaemia in vivo as targets for precision medicine

Total Cost €

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EC-Contrib. €

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Partnership

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Project "LeukaemiaTargeted" data sheet

The following table provides information about the project.

Coordinator
HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH 

Organization address
address: INGOLSTADTER LANDSTRASSE 1
city: NEUHERBERG
postcode: 85764
website: www.helmholtz-muenchen.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]
 Project website https://www.helmholtz-muenchen.de/ahs/team/detail/ma/6818/-Jeremias/index.html
 Total cost 1˙945˙818 €
 EC max contribution 1˙945˙818 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-08-01   to  2021-07-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH DE (NEUHERBERG) coordinator 1˙675˙510.00
2    LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN DE (MUENCHEN) participant 270˙308.00

Map

 Project objective

In Europe, around two million individuals die from cancer each year. Cancer is a genetic disease and each patient's tumour contains several genetic lesions which are identified by next generation sequencing (NGS) and influence patient's outcome. A global current challenge lies in translating NGS data into benefit of cancer patients. As attractive novel therapeutic concept, precision medicine addresses genetic lesions using targeted therapies. A large number of targeted drugs and compounds exist and are currently developed such as kinase inhibitors; unfortunately, numerous clinical trials on targeted therapies failed. In order to better exploit NGS data, it is important to discriminate between genetic lesions that are required and maintain patients' tumours in vivo and others that do not – an impossible mission so far. My proposal aims at solving this key question. Using acute leukaemia as model tumour disease, we propagate primary tumour cells from patients in immuno-deficient mice. We recently pioneered a worldwide unique technique which allows the distinct genetic manipulation of individual patients' tumour cells while they grow in vivo. We will molecularly target tumour-specific genetic lesions one by one; if tumour load is reduced, the lesion fulfils an essential function; essential lesions represent attractive therapeutic targets. Using our cutting edge technology, we will identify genetic lesions with essential, tumour-relevant function (i) in established tumour disease and (ii) in the clinically challenging situations of minimal residual disease and relapse. Our approach implements a new paradigm for target selection in oncology. Our work introduces molecular target validation as important step into the value chain of precision medicine which will tailor drug development by industry and academia. Our approach will improve patient care and the success rate of clinical trials for the benefit of patients suffering acute leukaemia and putatively other cancers.

 Publications

year authors and title journal last update
List of publications.
2019 Wen-Hsin Liu, Paulina Mrozek-Gorska, Tobias Herold, Larissa Schwarzkopf, Dagmar Pich, Kerstin Völse, Anna-Katharina Wirth, M. Camila Melo-Narváez, Michela Carlet, Wolfgang Hammerschmidt, Irmela Jeremias
KLF4 acts as a tumor suppressor in human B-cells and patients’ B-cell leukemias growing in mice
published pages: , ISSN: , DOI: 10.1101/737726
biorxiv.org 2019-10-03
2017 Susan Klaeger, Stephanie Heinzlmeir, Mathias Wilhelm, Harald Polzer, Binje Vick, Paul-Albert Koenig, Maria Reinecke, Benjamin Ruprecht, Svenja Petzoldt, Chen Meng, Jana Zecha, Katrin Reiter, Huichao Qiao, Dominic Helm, Heiner Koch, Melanie Schoof, Giulia Canevari, Elena Casale, Stefania Re Depaolini, Annette Feuchtinger, Zhixiang Wu, Tobias Schmidt, Lars Rueckert, Wilhelm Becker, Jan Huenges, Anne-Kathrin Garz, Bjoern-Oliver Gohlke, Daniel Paul Zolg, Gian Kayser, Tonu Vooder, Robert Preissner, Hannes Hahne, Neeme Tõnisson, Karl Kramer, Katharina Götze, Florian Bassermann, Judith Schlegl, Hans-Christian Ehrlich, Stephan Aiche, Axel Walch, Philipp A. Greif, Sabine Schneider, Eduard Rudolf Felder, Juergen Ruland, Guillaume Médard, Irmela Jeremias, Karsten Spiekermann, Bernhard Kuster
The target landscape of clinical kinase drugs
published pages: eaan4368, ISSN: 0036-8075, DOI: 10.1126/science.aan4368
Science 358/6367 2019-06-18
2018 Konstantinos Tzelepis, Etienne De Braekeleer, Demetrios Aspris, Isaia Barbieri, M. S. Vijayabaskar, Wen-Hsin Liu, Malgorzata Gozdecka, Emmanouil Metzakopian, Hamish D. Toop, Monika Dudek, Samuel C. Robson, Francisco Hermida-Prado, Yu Hsuen Yang, Roya Babaei-Jadidi, Dimitrios A. Garyfallos, Hannes Ponstingl, Joao M. L. Dias, Paolo Gallipoli, Michael Seiler, Silvia Buonamici, Binje Vick, Andrew J. Bannister, Roland Rad, Rab K. Prinjha, John C. Marioni, Brian Huntly, Jennifer Batson, Jonathan C. Morris, Cristina Pina, Allan Bradley, Irmela Jeremias, David O. Bates, Kosuke Yusa, Tony Kouzarides, George S. Vassiliou
SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-07620-0
Nature Communications 9/1 2019-05-10
2019 Jennifer R. Lynch, Basit Salik, Patrick Connerty, Binje Vick, Halina Leung, Aster Pijning, Irmela Jeremias, Karsten Spiekermann, Toby Trahair, Tao Liu, Michelle Haber, Murray D. Norris, Andrew J. Woo, Philip Hogg, Jianlong Wang, Jenny Y. Wang
JMJD1C-mediated metabolic dysregulation contributes to HOXA9-dependent leukemogenesis
published pages: , ISSN: 0887-6924, DOI: 10.1038/s41375-018-0354-z
Leukemia 2019-05-10
2017 I Tirado-Gonzalez, E Czlonka, A Nevmerzhitskaya, D Soetopo, E Bergonzani, A Mahmoud, A Contreras, I Jeremias, U Platzbecker, J P Bourquin, U Kloz, F Van der Hoeven, H Medyouf
CRISPR/Cas9-edited NSG mice as PDX models of human leukemia to address the role of niche-derived SPARC
published pages: 1049-1052, ISSN: 0887-6924, DOI: 10.1038/leu.2017.346
Leukemia 32/4 2019-05-10
2018 Ina-Katrin Siekmann, Kevin Dierck, Sebastian Prall, Marianne Klokow, Julia Strauss, Sophia Buhs, Antonina Wrzeszcz, Michael Bockmayr, Florian Beck, Magdalena Trochimiuk, Kristina Gottschling, Victoria Martens, Melissa Khosh-Naucke, Helwe Gerull, Jürgen Müller, Lena Behrmann, Martin Blohm, René P. Zahedi, Irmela Jeremias, Albert Sickmann, Peter Nollau, Martin A. Horstmann
Combined inhibition of receptor tyrosine and p21-activated kinases as a therapeutic strategy in childhood ALL
published pages: 2554-2567, ISSN: 2473-9529, DOI: 10.1182/bloodadvances.2018020693
Blood Advances 2/19 2019-05-10
2017 Anne-Kathrin Garz, Saskia Wolf, Sonja Grath, Verena Gaidzik, Stefan Habringer, Binje Vick, Martina Rudelius, Christoph Ziegenhain, Sylvia Herold, Marie-Theresa Weickert, Martha Smets, Christian Peschel, Robert A.J. Oostendorp, Sebastian Bultmann, Irmela Jeremias, Christian Thiede, Konstanze Döhner, Ulrich Keller, Katharina S. Götze
Azacitidine combined with the selective FLT3 kinase inhibitor crenolanib disrupts stromal protection and inhibits expansion of residual leukemia-initiating cells in FLT3-ITD AML with concurrent epigenetic mutations
published pages: , ISSN: 1949-2553, DOI: 10.18632/oncotarget.21877
Oncotarget 8/65 2019-05-10
2017 K Reiter, H Polzer, C Krupka, A Maiser, B Vick, M Rothenberg-Thurley, K H Metzeler, D Dörfel, H R Salih, G Jung, E Nößner, I Jeremias, W Hiddemann, H Leonhardt, K Spiekermann, M Subklewe, P A Greif
Tyrosine kinase inhibition increases the cell surface localization of FLT3-ITD and enhances FLT3-directed immunotherapy of acute myeloid leukemia
published pages: 313-322, ISSN: 0887-6924, DOI: 10.1038/leu.2017.257
Leukemia 32/2 2019-05-10
2018 Stefan Habringer, Constantin Lapa, Peter Herhaus, Margret Schottelius, Rouzanna Istvanffy, Katja Steiger, Julia Slotta-Huspenina, Andreas Schirbel, Heribert Hänscheid, Stefan Kircher, Andreas K. Buck, Katharina Götze, Binje Vick, Irmela Jeremias, Markus Schwaiger, Christian Peschel, Robert Oostendorp, Hans-Jürgen Wester, Götz-Ulrich Grigoleit, Ulrich Keller
Dual Targeting of Acute Leukemia and Supporting Niche by CXCR4-Directed Theranostics
published pages: 369-383, ISSN: 1838-7640, DOI: 10.7150/thno.21397
Theranostics 8/2 2019-05-10
2018 Birgitta Christine Heckl, Michela Carlet, Binje Vick, Catrin Roolf, Ameera Alsadeq, Michaela Grunert, Wen-Hsin Liu, Andrea Liebl, Wolfgang Hiddemann, Rolf Marschalek, Denis Martin Schewe, Karsten Spiekermann, Christian Junghanss, Irmela Jeremias
Frequent and reliable engraftment of certain adult primary acute lymphoblastic leukemias in mice
published pages: 1-4, ISSN: 1042-8194, DOI: 10.1080/10428194.2018.1509314
Leukemia & Lymphoma 2019-05-10
2017 Stefanie Göllner, Thomas Oellerich, Shuchi Agrawal-Singh, Tino Schenk, Hans-Ulrich Klein, Christian Rohde, Caroline Pabst, Tim Sauer, Mads Lerdrup, Sigal Tavor, Friedrich Stölzel, Sylvia Herold, Gerhard Ehninger, Gabriele Köhler, Kuan-Ting Pan, Henning Urlaub, Hubert Serve, Martin Dugas, Karsten Spiekermann, Binje Vick, Irmela Jeremias, Wolfgang E Berdel, Klaus Hansen, Arthur Zelent, Claudia Wickenhauser, Lutz P Müller, Christian Thiede, Carsten Müller-Tidow
Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia
published pages: 69-78, ISSN: 1078-8956, DOI: 10.1038/nm.4247
Nature Medicine 23/1 2019-05-10
2019 Fabian Koczian, Olga Nagło, Jan Vomacka, Binje Vick, Phil Servatius, Themistoklis Zisis, Britta Hettich, Uli Kazmaier, Stephan A. Sieber, Irmela Jeremias, Stefan Zahler, Simone Braig
Targeting the endoplasmic reticulum-mitochondria interface sensitizes leukemia cells to cytostatics
published pages: 546-555, ISSN: 0390-6078, DOI: 10.3324/haematol.2018.197368
Haematologica 104/3 2019-05-10
2019 Daniela Senft, Irmela Jeremias
A rare subgroup of leukemia stem cells harbors relapse-inducing potential in acute lymphoblastic leukemia
published pages: 1-10, ISSN: 0301-472X, DOI: 10.1016/j.exphem.2018.09.006
Experimental Hematology 69 2019-05-10
2018 Sannia Sarrach, Yuanchi Huang, Sebastian Niedermeyer, Matthias Hachmeister, Laura Fischer, Sebastian Gille, Min Pan, Brigitte Mack, Gisela Kranz, Darko Libl, Juliane Merl-Pham, Stefanie M. Hauck, Elisa Paoluzzi Tomada, Matthias Kieslinger, Irmela Jeremias, Antonio Scialdone, Olivier Gires
Spatiotemporal patterning of EpCAM is important for murine embryonic endo- and mesodermal differentiation
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-20131-8
Scientific Reports 8/1 2019-05-10

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