Explore the words cloud of the iAML-lncTARGET project. It provides you a very rough idea of what is the project "iAML-lncTARGET" about.
The following table provides information about the project.
|Coordinator Country||Germany [DE]|
|Total cost||1˙499˙750 €|
|EC max contribution||1˙499˙750 € (100%)|
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
|Duration (year-month-day)||from 2017-06-01 to 2022-05-31|
Take a look of project's partnership.
|1||MARTIN-LUTHER-UNIVERSITAET HALLE-WITTENBERG||DE (HALLE (Saale))||coordinator||1˙483˙275.00|
|2||MEDIZINISCHE HOCHSCHULE HANNOVER||DE (HANNOVER)||participant||16˙475.00|
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.
|year||authors and title||journal||last update|
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|
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|
Sina Al-Kershi, Raj Bhayadia, Michelle Ng, Lonneke Verboon, Stephan Emmrich, Lucie Gack, Adrian Schwarzer, Till Strowig, Dirk Heckl, Jan-Henning Klusmann
The stem cellâ€“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|
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
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 CRISPRâ€“Cas9 applications
published pages: 1375-1385, ISSN: 0305-1048, DOI: 10.1093/nar/gkx1268
|Nucleic Acids Research 46/3||2019-09-02|
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|
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
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 DÃ¶hner, Tobias MÃ¤tzig, Michelle Ng, Dirk Reinhardt, Hartmut DÃ¶hner, 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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