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iAML-lncTARGET SIGNED

Targeting the transcriptional landscape in infant AML

Total Cost €

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EC-Contrib. €

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Partnership

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 iAML-lncTARGET project word cloud

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

reflect    synergize    prognosis    aml    infant    incorporated    otherwise    basis    edit    diversity    coding    progression    therapeutic    sustaining    vulnerable    myeloid    resolve    innovative    achilles    renders    susceptibility    preclinical    overcome    probe    transcriptional    oncogenes    acute    highlighting    landscape    stage    prevalence    protein    inherited    biobank    shapes    oncogenic    create    aberrant    therapy    genome    enormous    transcriptomic    previously    interactome    rna    rnas    unfavorable    itself    establishing    drive    toxicities    origin    arising    predict    treatment    hypothesize    cancer    discovery    understand    hematopoietic    interventions    breakthroughs    leukemia    paradigm    cell    expertise    oncogene    cells    presumed    obstacles    chromatin    xenografts    shift    inducing    atlas    permissive    expression    maintaining    heel    standards    fetal    dismal    fertile    unrecognized    stem    transcriptome    programs    wastelands    patient    centered    despite    developmental    adult    background    diagnosis    transformation   

Project "iAML-lncTARGET" data sheet

The following table provides information about the project.

Coordinator
MARTIN-LUTHER-UNIVERSITAET HALLE-WITTENBERG 

Organization address
address: UNIVERSITAETSPLATZ 10
city: HALLE (Saale)
postcode: 6108
website: http://www.uni-halle.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 1˙499˙750 €
 EC max contribution 1˙499˙750 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-STG
 Funding Scheme ERC-STG
 Starting year 2017
 Duration (year-month-day) from 2017-06-01   to  2022-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MARTIN-LUTHER-UNIVERSITAET HALLE-WITTENBERG DE (HALLE (Saale)) coordinator 1˙483˙275.00
2    MEDIZINISCHE HOCHSCHULE HANNOVER DE (HANNOVER) participant 16˙475.00

Map

 Project objective

Infant acute myeloid leukemia (AML) has a dismal prognosis, with a high prevalence of unfavorable features and increased susceptibility to therapy-related toxicities, highlighting the need for innovative treatment approaches. Despite the discovery of an enormous number and diversity of transcriptional products arising from the previously presumed wastelands of the non-protein-coding genome, our knowledge of non-coding RNAs is far from being incorporated into standards of AML diagnosis and treatment. I hypothesize that the highly developmental stage- and cell-specific expression of long non-coding RNAs shapes a chromatin and transcriptional landscape in fetal hematopoietic stem cells that renders them permissive towards transformation. I predict this landscape to synergize with particular oncogenes that are otherwise not oncogenic in adult cells, by providing a fertile transcriptional background for establishing and maintaining oncogenic programs. Therefore, the non-coding transcriptome, inherited from the fetal cell of origin, may reflect a previously unrecognized Achilles heel of infant AML, which I will identify with my expertise to understand and edit the AML genome and transcriptome. I will apply recent breakthroughs from various research areas to i) create a comprehensive transcriptomic atlas of infant AML and fetal stem cells, ii) define aberrant or fetal stage-specific non-coding RNAs that drive leukemia progression, and iii) resolve their features to probe the oncogenic interactome. After iv) establishing a biobank of patient-derived xenografts, I will v) evaluate preclinical RNA-centered therapeutic interventions to overcome current obstacles in the treatment of infant AML. Targeting the vulnerable fetal stage-specific background of infant AML inherited from the cell of origin may set a paradigm shift for cancer treatment, by focusing on the permissive basis required by the oncogene for inducing and sustaining cancer, rather than on the oncogene itself.

 Publications

year authors and title journal last update
List of publications.
2019 Michelle Ng, Dirk Heckl, Jan-Henning Klusmann
The Regulatory Roles of Long Noncoding RNAs in Acute Myeloid Leukemia
published pages: , ISSN: 2234-943X, DOI: 10.3389/fonc.2019.00570
Frontiers in Oncology 9 2020-01-30
2019 Michaela Kuhlen, Jan-Henning Klusmann, Jessica I. Hoell
Molecular Approaches to Treating Pediatric Leukemias
published pages: , ISSN: 2296-2360, DOI: 10.3389/fped.2019.00368
Frontiers in Pediatrics 7 2020-01-30
2019 Sina Al-Kershi, Raj Bhayadia, Michelle Ng, Lonneke Verboon, Stephan Emmrich, Lucie Gack, Adrian Schwarzer, Till Strowig, Dirk Heckl, Jan-Henning Klusmann
The stem cell–specific long noncoding RNA HOXA10-AS in the pathogenesis of KMT2A-rearranged leukemia
published pages: 4252-4263, ISSN: 2473-9529, DOI: 10.1182/bloodadvances.2019032029
Blood Advances 3/24 2020-01-30
2020 Sarah Grasedieck, Christoph Ruess, Kathrin Krowiorz, Susanne Lux, Nicole Pochert, Adrian Schwarzer, Jan-Henning Klusmann, Mojca Jongen-Lavrencic, Tobias Herold, Lars Bullinger, Jonathan R. Pollack, Arefeh Rouhi, Florian Kuchenbauer
The long non-coding RNA Cancer Susceptibility 15 is induced by Isocitrate Dehydrogenase mutations and maintains an immature phenotype in adult acute myeloid leukemia
published pages: haematol.2019.23, ISSN: 0390-6078, DOI: 10.3324/haematol.2019.235291
Haematologica 2020-01-30
2017 Maurice Labuhn, Felix F Adams, Michelle Ng, Sabine Knoess, Axel Schambach, Emmanuelle M Charpentier, Adrian Schwarzer, Juan L Mateo, Jan-Henning Klusmann, Dirk Heckl
Refined sgRNA efficacy prediction improves large- and small-scale CRISPR–Cas9 applications
published pages: 1375-1385, ISSN: 0305-1048, DOI: 10.1093/nar/gkx1268
Nucleic Acids Research 46/3 2019-09-02
2018 Marius Flasinski, Kira Scheibke, Martin Zimmermann, Ursula Creutzig, Katarina Reinhardt, Femke Verwer, Valerie de Haas, Vincent H. J. van der Velden, Christine von Neuhoff, C. Michel Zwaan, Dirk Reinhardt, Jan-Henning Klusmann
Low-dose cytarabine to prevent myeloid leukemia in children with Down syndrome: TMD Prevention 2007 study
published pages: 1532-1540, ISSN: 2473-9529, DOI: 10.1182/bloodadvances.2018018945
Blood Advances 2/13 2019-09-02
2018 Mareike Rasche, Martin Zimmermann, Lisa Borschel, Jean-Pierre Bourquin, Michael Dworzak, Thomas Klingebiel, Thomas Lehrnbecher, Ursula Creutzig, Jan-Henning Klusmann, Dirk Reinhardt
Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012
published pages: 2167-2177, ISSN: 0887-6924, DOI: 10.1038/s41375-018-0071-7
Leukemia 32/10 2019-09-02
2018 Raj Bhayadia, Kathrin Krowiorz, Nadine Haetscher, Razan Jammal, Stephan Emmrich, Askar Obulkasim, Jan Fiedler, Adrian Schwarzer, Arefeh Rouhi, Michael Heuser, Susanne Wingert, Sabrina Bothur, Konstanze Döhner, Tobias Mätzig, Michelle Ng, Dirk Reinhardt, Hartmut Döhner, C. Michel Zwaan, Marry van den Heuvel Eibrink, Dirk Heckl, Maarten Fornerod, Thomas Thum, R. Keith Humphries, Michael A. Rieger, Florian Kuchenbauer, Jan-Henning Klusmann
Endogenous Tumor Suppressor microRNA-193b: Therapeutic and Prognostic Value in Acute Myeloid Leukemia
published pages: 1007-1016, ISSN: 0732-183X, DOI: 10.1200/JCO.2017.75.2204
Journal of Clinical Oncology 36/10 2019-06-13

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