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Information für die Wissenschaft Nr. 05 | 31. Januar 2013
Priority Programme “Epigenetic Regulation of Normal Hematopoiesis and its Dysregulation in Myeloid Neoplasia” (SPP 1463)

The Senate of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) has established in 2009 a Priority Programme (Schwerpunktprogramm, SPP), entitled “Epigenetic Regulation of Normal Hematopoiesis and its Dysregulation in Myeloid Neoplasia”. The Priority Programme has been running, with 15 funded groups within Germany, since 2011. It runs for a period of up to six years and the main aim is to investigate mechanisms of epigenetic control of normal myeloid development and their disturbances in myeloid cancers, both in vitro and in vivo.

Epigenetic research, i.e. the evaluation of heritable gene expression patterns without changes in the DNA sequence, has primarily focussed on the regulation of highly coordinated developmental changes of cells and organisms, as well as disturbances of epigenetic mechanisms in hereditary and acquired human diseases, including cancer. Significant interest arises in the therapeutic potential of epigenetic mechanisms. In contrast to cancer-specific genetic alterations (mutations), cancer “epimutations” (i.e. functional gene inactivations) are pharmacologically reversible. The myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), constituting a biological continuum, have emerged as model diseases to study tumour (epi-)genomes and epigenetic therapy. AML is a rare tumour with a dismal prognosis in the majority of the (often elderly) patients inflicted, and thus poses a highly unmet clinical need.

Currently, three research areas merge in cancer epigenetics, hematopoiesis, and myeloid malignancies:

  • The advances in “deep sequencing” technology now permit genome-wide analyses of multiple epigenetic events on an unprecedented scale.

  • A wealth of information on enzymatic epigenetic mechanisms has arisen in recent years. What lies ahead is to identify and manipulate specific epigenetic mechanisms that are at work in cancer cells, and to explore applicability for diagnostic, therapeutic and prognostic approaches.

  • Epigenetic drugs have recently been approved for the treatment of myeloid malignancies. The clinical experience with these drugs as well as the possibility to analyse the clinical specimens, with regard to changes in epigenetic markers, is crucial for the understanding and utilisation of epigenetic strategies in myeloid malignancies.

The goal of this Priority Programme is to enhance and to accelerate these merging fields, and to shape the future of epigenetic research and therapy in the myeloid system. Six highly relevant research aims for this Programme have been identified:

  • to define the epigenome of normal and myeloid leukemic hematopoietic cells by

  • (epi-)genomewide, global profiling techniques

  • to dissect the epigenetic regulation of hematopoietic stem cell and myeloid differentiation

  • to investigate the role of key myeloid transcription factors as epigenetic modifiers

  • to search for novel epigenetic lesions in primary myeloid leukemia and preleukemia

  • to develop preclinical models of epigenetic therapy of myeloid neoplasias

  • to study the in vivo changes mediated by epigenetic therapy of myeloid neoplasias (i.e. hypomethylating agents, inhibitors of HDACs and other chromatin-modifying enzymes)

To endow the Priority Programme with a strong focus, applications should fall within the following areas of research:
Epigenetic research, defined as the study of:

  • DNA methylation

  • posttranslational histone modifications

  • enzymatic mechanisms of normal and transformed myeloid epigenesis

  • RNA methylation (insofar as it relates to gene expression)

These mechanisms will be investigated in models of normal myeloid differentiation and of myeloid leukemia and preleukemia:

  • normal granulocytes, monocytes and their precursors

  • their neoplastic counterparts, i.e. acute myeloid leukemias, represented by cell line models and primary transformed human cells

  • animal models of myeloid leukemias and preleukemias

The following research questions should be excluded:

  • lymphoid malignancies and normal lymphoid development

  • solid tumours (animal models, cell lines and primary tumours)

The following research questions should also be excluded, unless directly linked to epigenetic mechanisms:

  • myeloid gene regulation on the transcriptional level

  • myeloid-specific oncofusion proteins that are not directly linked to epigenetic alterations

  • murine models of myeloid leukemia not representative of epigenetic disturbances

  • DNA damage and repair as mechanisms leading to chromosomal instability or chromosomal rearrangements (unless studied in the context of epigenetic therapy of myeloid neoplasia)

  • nuclear structures and chromatin topology

  • nuclear reprogramming or cell fusion

  • non-coding RNAs

  • cell cycle regulation, apoptosis, senescence, autophagy etc. without a direct link to epigenetic mechanisms

  • drug development targeting non-epigenetic modifications in myeloid leukemia (e.g. activated tyrosine kinases and other frequently disturbed signalling pathways)

Proposals for the second three-year funding period can be submitted until May 15, 2013 (deadline) through the DFG’s electronic proposal processing system “elan”. In this system please select “SPP 1463” when submitting your proposal. All proposals must be written in English and written according the DFG Proposal Preparation Instructions (DFG Form 54.01). Please include a title page with your name, your address, and the title of your project in your application.
In addition, please submit the proposal and the CV of the principle investigators on paper in triplicate to the DFG. Please do not submit any other documents on paper.

The review will be held during a proposal colloquium scheduled to take place in Freiburg/Br. in September 2013.

Further information

The DFG’s electronic portal “elan” can be found at:

Proposal guidelines and preparation instructions are outlined in DFG forms 54.01en and 50.05en, part B which can be found on the DFG’s website at:

For further information please refer to the Priority Programme’s webpage:

For further scientific information, please contact the Priority Programme’s coordinators:

  • Prof. Dr. med. Michael Lübbert,
    Abt. Hämatologie und Onkologie, Medizinische Klinik,
    Universitätsklinikum Freiburg,
    Hugstetter Str. 55,
    79106 Freiburg,
    phone +49 761 270-35340,
    fax +49 761 270-36970,
    Michael.Luebbert@uniklinik-freiburg.de

  • Prof. Dr. rer. nat. Christoph Plass,
    C010 – Epigenomik und Krebsrisikofaktoren,
    Deutsches Krebsforschungszentrum,
    Im Neuenheimer Feld 280,
    69120 Heidelberg,
    phone +49 6221 42-3300,
    fax +49 6221 42-3359,
    C.Plass@dkfz.de

For administrative enquiries please contact:

  • Dr. Eckard Picht,
    Deutsche Forschungsgemeinschaft (DFG),
    Lebenswissenschaften 1,
    53170 Bonn,
    phone +49 228 885-2028,
    fax +49 228 885-2777,
    Eckard.Picht@dfg.de

  • Jutta Nehler,
    Deutsche Forschungsgemeinschaft (DFG),
    Lebenswissenschaften 1,
    53170 Bonn,
    phone +49 228 885-2535,
    fax +49 228 885-2777,
    Jutta.Nehler@dfg.de

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