The aim of the SALL program is to study fundamental and clinical aspects of stem cells, leukemia and lymphoma by incorporating various disciplines with state-of-the-art technologies and -omics approaches. The focus comprises the full range of basal, applied, translational and clinical research topics. The weekly meetings provide an excellent learning environment for PhD students and facilitate interactions between clinicians and basic scientists with different backgrounds. The PIs and other members of the SALL program are appointed at various departments, i.e. Hematology, Pathology & Medical Biology, Pediatric Oncology, Cell Biology and the European Institute for the Biology of Ageing (ERIBA). The aim is to cover the entire spectrum “from bench to bed”. This is achieved by the broad range of expertise of the PIs, from clinical to translational and fundamental topics, resulting in a multidisciplinary research group.
The stem cell research lines focus on how blood cell development is regulated during normal hematopoiesis, and during ageing. Most studies are aimed at identifying mechanisms and genes that specify hematopoietic stem cell self-renewal, using the mouse as a model system. Also, the flatworm is used as a model to understand the fundamental mechanisms underlying regulation of stem cell activity during ageing, and human stem cells (hematopoietic and otherwise) are studied in detail as well. Stem cell purification, transplantation, genetic perturbation, transcriptional profiling and epigenetic screenings are key instruments in these studies.
The leukemia research lines have a clear focus on leukemic stem cells and leukemia development in children and adults. Primary human hematopoietic stem/progenitor cells and leukemic cells from patients are manipulated by a variety of cell biological and molecular techniques to deepen the insights in the development of human leukemia. One of the aims is to identify leukemia-specific plasma membrane markers using transcriptomics and proteomics in order to detect, target and ultimately eradicate leukemic stem cells. Another topic is to investigate how normal young and old stem cells are affected by intervention of chemotherapy and transplantation, and via which mechanisms the process of ageing contributes to the development of hematological malignancies. Finally, there is a focus on how alterations in the microenvironment and angiogenesis are linked to leukemic progression and resistance. The results of all these studies are translated into clinical studies.
The lymphoma research lines focus on the most common B-cell lymphoma types and aim to deepen the insight into the pathogenetic mechanisms of lymphoid malignancies. The research topics include genetic aberrations and susceptibility, interaction between the tumor cell and its microenvironment, serological biomarkers and on the role of non-coding RNAs. Another aspect studied is how ageing of the immune system, and especially of the B-cell compartment, contributes to development of specific B-cell lymphoma subtypes. These B-cells most likely escape from apoptosis due to accumulation of genetic and epigenetic aberrations over time. Results from these fundamental studies are translated into clinical studies such as testing their value as diagnostic criteria for classification, using biomarkers for treatment response and prognostication and late treatment-related toxicity. These studies are conducted in close collaboration with the (inter)national working parties for lymphoma and leukemia within HOVON and EORTC.