The research group led by  professor Peter Hokland addresses translational aspects of leukemogenesis primarily in myeloid malignancies. For the past decade, the concept of minimal residual disease (MRD) has been a major focus, and we have been performing comprehensive research aimed at showing a better understanding of the depth of MRD in both acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Here, MD PhD Peter Niekerk recently showed that  a combination of  fluorescence activated cell sorting (FACS) and fluorescence in situ hybridization (FISH) analysis, MRD can be assessed at  stem cell level in CML patients in deep molecular remission. In an ongoing project supported by the Danish Cancer Society , MD PhD Hans Beier Ommen and MSc PhD-student Anita Tranberg Simonsen are investigating clonal evolution and MRD in AML and CML during treatment and follow-up. The study includes an evaluation of the quality of life of  patients followed on an extended outpatient basis.

Increasing evidence from international research shows that many hematological malignancies are maintained by a very small subset of cells with stem cell features called leukemic stem cells (LSC). Such LCSs are believed to be enriched in MRD and to be responsible for relapse in AML. In our group, MSc PhD Anni Aggerholm has demonstrated the persistence of DNMT3A mutations in adult  patients with AML in long-term remission, indicating the existence even of pre-leukemic stem cells. Thus, in natural continuation of our former and ongoing research, we are also aiming at developing new tools for identifying putative LSCs and ways to isolate such cells for immunophenotypic, cytogenetic, molecular and functional analyses.

In AML, MD PhD Anne Stidsholt Roug has identified the human Myeloid Inhibitory C-type lectin-like receptor (hMICL) as a valid MRD and LSC marker. Currently, PhD-student Laura Laine Herborg is investigating whether hMICL may also be a surrogate marker revealing underlying molecular aberrations in AML. Moreover, we have introduced aldehyde dehydrogenase (ALDH) as a putative LSC marker in our experimental work to refine the characterization and isolation of LSCs. MSc PhD Line Nederby and MD PhD-student Marie Toft-Petersen are currently evaluating ALDH/hMICL/CD123 as an assembled and reliable marker of LSCs in both AML and myelodysplastic syndrome. The methodology is based on immunophenotyping, cell sorting and functional analyses of cell subfractions in long-term cultures. Furthermore, in collaboration with MSc Marcus Celik Hansen, we are elucidating the heterogeneity in a smaller proportion of these sorted LSC-fractions by performing gene expression analyses on  single cell level.