Epigenetic Regulation of normal hematopoiesis and its dysregulation in myeloid neoplasia

Epigenetic Regulation of normal hematopoiesis and its dysregulation in myeloid neoplasia

Cancer Epigenomics is a research area that drives the development of novel and innovative methodologies to study genome-wide epigenetic patterns, drug discovery and development, and novel therapeutic approaches targeting the cancer-specific epigenetic defects. Here myeloid cancers such as acute myeloid leukemia (AML) and the preleukemic myelodysplastic syndromes (MDS) have emerged as model diseases to study the cancer (epi)genome.

The cancer epigenetics field, especially in hematopoiesis and myeloid malignancies, has reached a corner stone by the merge of three research areas.

Firstly, technological advances allow genome-wide identification and characterization of epigenetic alterations in myeloid cells.

Secondly, the recent increase in the understanding of epigenetic mechanisms in non-transformed cells leads to the challenge of identifying and determining the specific epigenetic mechanisms at work in cancer cells and their applicability for diagnostic, therapeutic and prognostic approaches.

Thirdly, the clinical experience with drugs now being in the process of approval for therapy as well as the possibility to analyze clinical specimens with regard to changes in epigenetic markers will be crucial to understand and utilize epigenetic strategies in myeloid malignancies.

These three increasingly overlapping research areas lead to the emerging new field: Epigenetic events and therapy in myelopoiesis and myeloid malignancy.

This Priority Program is intended to contribute to a better understanding of epigenetic mechanisms regulating gene expression in normal hematopoiesis and myeloid neoplasia (focussing on acute myeloid leukemia and myelodysplastic syndromes), and to translate this understanding into novel and effective therapies. To achieve this goal, we have formulated the following five aims of the Program:

  • to define the epigenome of normal and myeloid leukemic hematopoietic cells by (epi)genome-wide, global profiling techniques
  • to dissect epigenetic regulation of hematopoietic stem cell protection and myeloid differentiation
  • to investigate the role of key myeloid transcription factors and of myeloid leukemia-specific fusion genes as epigenetic modifiers
  • to search for novel genetic and epigenetic lesions in primary myeloid leukemia and preleukemia
  • to develop preclinical models of epigenetic therapy of myeloid neoplasias