Manja Wobus, Eric So
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. It is a hematological malignancy arising from the occurrence of genetic mutations in clonal hematopoietic progenitors, which cause a block in differentiation and an uncontrolled growth of leukemic blasts in the bone marrow. Besides directly targeting the leukemic cells other approaches aim to identify and target common features within this complex disease.
One potential target is the bone marrow microenvironment, which is the site where leukemic cells arise, expand, and eventually develop resistance to therapy. Recent findings indicate that myeloid malignancies also affect the function of the bone marrow niche, pointing to the existence of an active crosstalk between leukemic cells and the microenvironment. Thus far, comprehensive analyses of the molecular and metabolic changes in AML bone marrow mesenchymal stromal cells (MSC) of larger patient cohorts are sparse.
Profiting from the long-term cooperation between Prof. Eric So, head of the Leukemia and Stem Cell Biology section at King’s, and PD Dr. Manja Wobus from the Department of Haematology/Oncology at TUD, the project aims at applying the joint expertise on MSC biology for investigations of metabolic changes in distinct types of AML, such as MLL- and NPM1c-AML. The complementary research projects will achieve maximal synergism between both institutions by extensive characterization of the leukemic clone and stromal environment from the same patient sample. It offers the unique chance to combine a multidimensional omics analysis of both the leukemic clone and the stromal microenvironment. The projects is divided into two work packages, whereas the first focuses on the metabolic analyses of one marrow stromal cells, plasma and peripheral blood, the second will go into detail on the evaluation of MSC metabolic activity.