The German Federal Ministry of Education and Research (BMBF), has transferred €2.45m to a research collaborative known as LeukoSyStem to “get to the root of the problem” of leukemia. With an emphasis on stem cell research and “the starting point of leukemia,” the collaborative involves prominent research groups within Germany, including scientists at Heidelberg University Hospital (UKHD), the Heidelberg Institute for Stem Cell Technology and Experimental Medicine at the German Cancer Research Center (HI-STEM/DKFZ), the German Cancer Research Center (DKFZ) and the European Molecular Biology Laboratory (EMBL).
Leukemia stem cells are thought to be the starting point of leukemia. Hence, the ability to eliminate them is an underlying premise for successful long-term therapy. This team will investigate the cells that are the origin of acute myeloid leukemia (AML) with the hopes of generating a greater understanding of how to ultimately develop cell therapy-based treatments.
The team will collect patient samples, in the form of isolated single cells, at various locations and investigate characteristic markers, mutations, functional data, and metabolic pathways all to progress the understanding of leukemia stem cells and their environment in the bone marrow. The team will employ specialized, tailored computer algorithms to support the evaluation of all samples.
Eliminate Leukemia at the Source: Leukemia Stem Cells
Normal healthy blood cells start from hematopoietic stem cell in the bone marrow and proceeds through various stages of so-called precursor cells. At each of these stages, according to the German Cancer Research Center press release, the accumulation of mutations can lead to cell degeneration and the development of blood cancer (leukemia). AML is the most common form of leukemia in adults and is represented by mutated, functionless blood cells (blasts) that overgrow and take over other bone marrow cells. Five out of 100,000 people receive a diagnosis of AML in Europe. Despite advancing therapeutic options (ranging from chemotherapy to stem cell transplantation), relapses are frequent and the five-year survival rate for patients up to the age of 60 is 35-40%. For patients above 60, it is only 5-10%.
The Premise of this Research
The research funder’s underlying premise rests on the assumption that an effective cure of leukemia patients centers on the targeted elimination of the leukemia’s starting cells, called leukemia stem cells. Dr. med. Simon Raffel, project partner from the Department of Hematology, Oncology and Rheumatology at UKHD, commented, “For therapy, we need to find the cause of the problem and tackle leukemia stem cells.”
The Study Segments
Scientists still don’t fully understand the interaction of leukemia stem cells with other factors and cells of the stem cell niche (in the bone marrow). The LeukoSyStem “junior research alliance” will organize itself into three sub-projects or studies including: 1) the analysis of single leukemia stem cells, 2) an investigation of the stem cell niche in the bone marrow, and 3) a systems medical, comprehensive evaluation of the collected data.
Attack the Cancerous Cells while Sparing the Healthy Cells
These European-based researchers are particularly interested in the ability to distinguish between healthy and leukemia stem cells, as this is only possible to a limited extent using existing biomarkers. Only when this can be done more precisely can new biomarkers for the discovery of the mutated cells be identified, opening up new points of attack for targeted therapies. As Dr. Raffel notes, “The treatment of AML will be all the more successful the more precisely we can specifically eliminate the leukemia’s starting cells and spare the healthy blood cells in the future.”
The BMBF-originated public funding goes to the collaborative alliance LeukoSyStem; a group of young scientists/investigators from the identified research institutions in Europe. This project commenced at the start of 2020 and equals a total of €2.45 million over five years; Approximately €1.3 million are allocated for the Department of Hematology, Oncology and Rheumatology at UKHD.
The funds for this initiative are allocated to researchers as part of the “junior” alliance called LeukoSyStem. Led by Dr. Simon Hass of HI-STEM/DKFZ, the initiative centers on the systemic mapping of the leukemia stem cell microenvironment by combined single-cell and spatial transcriptomics.
Dr. med. Simon Raffel, project partner from the Department of Hematology, Oncology and Rheumatology at UKHD
Prof. Dr. Carsten Muller-Tidow, Medical Director, UKHD
Dr. Simon Haas (HI-STEM/DKFZ)
Dr. Laleh Haghverdi, EMBL
Call to Action: Interested in stem cell-level research centering on leukemia with an emphasis on AML? This European-based research team will be diving deep into this topic and represents an important research network. Those interested in similar topics should consider connecting.