SFB 1243

Cancer Evolution: Genetic and Epigenetic Evolution of Hematopoietic Neoplasms

The goal of the SFB 1243 is to investigate different aspects of cancer evolution, in particular the poor prognosis of acute myeloid leukemia and indolent lymphomas, using an interdisciplinary approach including natural sciences, clinical sciences and computational biology.

Within the SFB consortium the ICB will work on the project A17 "Computational models of neoplasmic heterogeneities and lineage choice".
Acute myeloid leukemia (AML) often results from the myelodysplastic syndrome (MDS). Here, the differentiation hierarchy from hematopoietic stem cells to mature, functional cells is disturbed. AML patients, again, frequently carry a mixture of different cancer cell types, so-called subclones. This is reflected by a mixture of genomic signatures and heterogeneous transcriptome profiles. Applying statistical and dynamical models to data from our clinical and biological collaborators in this SFB, we want to identify altered differentiation hierarchies of MDS subclones and characterize the development of related heterogeneities in AML while the tumor undergoes evolution.

Figure legend: Objectives of this project. Left: Inferring transcriptional and genomic heterogeneity in AML, that is the co-existence of at least two distinct cell populations within a tumor, and how it evolves over time. Right: Estimating differentiation and self-renewal rates in healthy and clonal differentiation hierarchies from healthy and MDS patent data.

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