Langen Science Award 2019 to Prof. Daniela Krause for research on new therapeutic target for leukaemia

The six-person prize committee, chaired by former President of the PEI, Prof. Johannes Löwer, had shortlisted five candidates from among the applications for the Langen Science Award and invited the relevant researchers to a public lecture event at the PEI in September. The other committee members are Professor Klaus Cichutek, President of the PEI, Frieder Gebhardt, Mayor of Langen, Manfred Pusdrowski, CEO of Stadtwerke Langen, Professor Hansjörg Schild, Institute of Immunology, Mainz, and Professor Erhard Seifried, German Red Cross Blood Transfusion Service Baden-Württemberg/Hesse.

Professor Daniela Krause was shortlisted for the prize based on her research on „Home is where the bone is – the bone marrow environment as an influencing factor and innovative therapeutic approach in normal and malignant haematopoiesis“. Professor Krause and her team carry out research into the bone marrow microenvironment in normal haematopoiesis and in haematopoiesis in leukaemia patients. The intention is to use therapeutic targets and combine them with established cancer therapies in order to improve the efficacy of treatment.

Following a longstanding tradition, this year’s prize winner will also be visiting a Langen school to report on her research.

About Professor Daniela Krause’s Research
Leukaemia – also known as blood cancer – originates in cells of the bone marrow, the site where blood is formed. Acute leukaemia can occur at any age, while chronic leukaemia is particularly common in adults. Current therapies often fail to eliminate the leukaemia stem cells that are responsible for the progression of the cancer and its recurrence. Leukaemia cells contain a proportion of cancer stem cells that lead to the replication of leukaemia cells. They interact with the microenvironment of the bone marrow, a complex of very diverse cell types, as well as with the extracellular matrix and the physical environment. As a result of these interactions, the cancer stem cells in particular are often able to evade conventional cancer therapies.

Professor Daniela Krause and her team are conducting research into the role of the bone marrow microenvironment in normal haematopoiesis as well as in malignant – leukaemia-associated – haematopoiesis. They are looking for suitable inhibitors that will specifically disrupt the interactions of the leukaemia cells with the bone marrow microenvironment. The goal is to combine these inhibitors of tumour environment interaction with established cancer therapies in order to develop effective therapies for eliminating dangerous leukaemia stem cells. To achieve this, the scientists are pursuing various approaches. For example, in recent research they showed that mice with a specific form of leukaemia who were treated with an inhibitor of the surface protein E-selectin in combination with the tyrosine kinase inhibitor imatinib survived significantly longer than mice who received only imatinib. The surface protein E-selectin is found on vascular cells.

Another focus of their research is vitamin K antagonists and their influence on haematopoiesis; vitamin K antagonists are used worldwide for the prevention of thromboses. In the context of this research, the research group found that treating haematopoietic stem cells with periostin prior to allograft stem cell transplantation (transplantation of stem cells from another donor) results in improved implantation of the transplanted haematopoietic stem cells. Periostin is a component of the extracellular matrix and plays a role in cell migration, proliferation, survival and adhesion. The research group holds a patent for this innovative therapeutic approach. Professor Krause and her colleagues have also identified a cell cycle regulator and apoptosis inhibitor in leukaemia with the protein FUBP1 (far upstream element binding protein 1). Other approaches used by Professor Krause’s research group, some of which have also been patented, target the therapeutic modulation of the cellular and non-cellular components of the bone marrow microenvironment with the goal of bringing these new research findings into clinical application as quickly as possible.

Selected publications

Krause DS, Fulzele K, Catic A, Sun CC, Dombkowski D, Hurley MP, Lezeau S, Attar E, Wu JY, Lin HY, Divieti-Pajevic P, Hasserjian RP, Schipani E, Van Etten RA, Scadden DT (2013). Differential regulation of myeloid leukemias by the bone marrow microenvironment. Nature Medicine; 19(11):1513-1517
doi: 10.1038/nm.3364

Verma D, Kumar R, Pereira RS, Karantanou C, Zanetti C, Minciacchi VR, Fulzele K, Kunst K, Hoelper S, Zia-Chahabi S, Jabagi M-J, Emmerich J, Dray-Spira R, Kuhlee F, Hackmann K, Schroeck E, Wenzel P, Müller S, Filmann N, Fontenay M, Divieti-Pajevic P, Krause DS (2019). Vitamin K-antagonism impairs the bone marrow microenvironment and hematopoiesis. Blood., 134(3):227-238
doi: 10.1182/blood.2018874214

Godavarthy PS, Kumar R, Herkt SC, Pereira RS, Hayduk N, Weissenberger ES, Aggoune D, Manavski Y, Lucas T, Pan K-T, Voutsinas JM, Wu Q, Müller MC, Saussele S, Oellerich T, Oehler VG, Lausen J, Krause DS
The vascular bone marrow niche influences outcome in chronic myeloid leukemia via the E-selectin – SCL/TAL1 – CD44 axis
Haematologica. 2019 Apr 24. pii: haematol.2018.212365. doi: 10.3324/haematol.2018.212365

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