Projects of the AG Damm

Currently, the AG Damm focuses on the following research projects:

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Clonal hematopoiesis of indeterminate potential (CHIP)

Clonal hematopoiesis of indeterminate potential (CHIP) occurs in an age-related manner and associates with an increased risk of hematologic cancer, atherosclerotic disease and shorter overall survival. Approximately one third of the population above 60 years of age harbor somatic mutations in the peripheral blood. These aberrations commonly affect epigenetic regulators of transcription (DNMT3A, TET2, and ASXL1). Clinical consequences of this novel phenomenon remain only partially understood and caution is warranted to understand CHIP in all its bearings. We systematically investigate the cell of origin, cellular repartition patterns, clonal dynamics, and associated methylation/transcriptional changes in different well-defined clinical settings. Furthermore, we are interested in functional consequences of these mutations and develop an in vitro model using CRISPR/Cas technology to mick cellular aging processes.  

Arends CM, Galan-Sousa J, Hoyer K, …, Damm F. Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis. Leukemia (2018). doi:10.1038/s41375-018-0047-7

Involvement of multipotent progenitor cells in lymphoid malignancies

We have revealed that somatic mutations may occur in the stem/ progenitor cell compartment of patients with chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in Western countries. Our work advocates for abnormalities in early B-cell differentiation as a phenotypic convergence of the diverse acquired mutations observed in CLL. These observations may have an impact on the follow-up and treatment of patients with CLL. It will therefore be important to understand how these findings relate to the clinical evolution of the patients and to what extent they also apply to other mature lymphoid malignancies.

Damm F, Mylonas E, Cosson A, et al. Acquired Initiating Mutations in Early Hematopoietic Cells of CLL Patients. Cancer Discovery 4, 1088–1101 (2014). doi:10.1158/2159-8290.CD-14-0104

Phylogeny and clonal evolution of hematologic malignancies

Clonal heterogeneity plays an important role in therapy response and disease relapse. Evolutionary plasticity, cellular context and type of gene aberrations impose limitations on current treatment approaches. Using single cell technologies, we perform detailed clonal heterogeneity tracking studies. We profile temporally as well as spatially separated samples to quantify changing clonal phylogenies, during disease progression, or in response to therapeutic intervention.

Fish plot showing the clonal progression during course of disease.