Members of Hematology and Immunology (HEIM) are involved in basic and clinical research in the broad field of hematology. Basic research includes cellular and molecular biology of multiple myeloma, molecular and phenotypic characterization of leukemic cells, NK cell activity in leukemia, characterization of hematopoietic and mesenchymal stem cells, pathogenesis of thrombophilia. Clinical research is focused on the participation in phase II-IV clinical trials including patients with all major hematological malignancies. Multiple myeloma is a major research topic of the group covering the spectrum from in vitro molecular and cellular studies, the development of a world-wide validated mouse model for the study of myeloma pathogenesis and preclinical drug development, translational research involving dendritic cell therapy and clinical trials for early as well as advanced disease. The Myeloma Centre Brussels is internationally recognized in the field.
- to offer a platform for academic collaboration and cross “pollination” for clinicians and scientists in the broad field of hematology
- to apply results from basic research into clinical applications including innovative diagnostic tools and novel therapeutic or supportive care strategies
- Identification of the drug resistant tumor population in myeloma (Els VanValckenborgh, Karin Vanderkerken)
- Epigenetic regulation of the myeloma cells (Elke De Bruyne, Karin Vanderkerken)
- Presence of NKT cells and how they can be activated in a residual myeloma setting (Eline Menu, Karin Vanderkerken)
- The influence of the bone marrow microenvironment on the survival, growth and drug resistance of the myeloma cells (Eline Menu, Els Van Valckenborgh, Elke De Bruyne, Karin Vanderkerken, in collaboration with Ivan van Riet )
- Biology and therapeutical potential of mesenchymal stem cells (Ivan Van Riet, Ann De Becker,in collaboration with Karin Vanderkerken)
- Evaluation of new clinical transplantation and cell processing protocols using blood- and bone marrow derived stem cells (Rik Schots, Ivan Van Riet)
- Minimal residual disease assessment in acute lymphoblastic leukemia for evaluation of therapeutic response (Marleen Bakkus)
- Study on the anti-leukemic activity of donor Natural Killer cell KIR genes in hematopoietic stem cell transplantation (Christian Demanet, Sonja Verheyden).
- Characterisation of hematopoietic precursor cells in myelodysplastic syndromes and myeloproliferative disorders. (Marc De Waele, Kristin Jochmans, Fabienne Trullemans)
- Characterisation of anti-thrombin III deficiency (Kristin Jochmans, Marc De Waele)
Relevant observations and perspectives
Phenotypic and molecular research of the myeloma cell has contributed to the knowledge of the natural differentiation of B cells into plasma cells and the molecular events leading to malignancy as well as genetic alterations during disease progression. The surface membrane expression of specific tumor antigens is a marker of this derailment. This knowledge has led to the development of diagnostic and prognostic tools.
The myeloma cell growth and homing is mediated by reciprocal interactions with the bone marrow microenvironment, consisting of stromal cells, immunological cells and extracellular matrix proteins. This mutual communication with the bone marrow causes bone destruction (osteolysis) and angiogenesis. Intervening with these interactions is part of the development of new therapeutical strategies. The presence of a unique mouse model for MM in our laboratory permits preclinical assays of new molecules and experimental cell therapy approaches which can be further validated in clinical trials.
Myelodysplastic syndromes are hematopoietic precursor neoplasms characterized by cytopenia in the peripheral blood and dysplastic features of the bone marrow cells. Hematopoietic precursors can be identified by their expression of the CD34 antigen. In the majority of cases the CD34 positive cells in myelodysplastic syndromes show immunophenotypic abnormalities compared with CD34 positive cells of normal donors and of patients with secondary (nonmalignant) cytopenia. These abnormalities are more pronounced in more advanced stages and are similar to those found in acute myeloid leukaemia. These findings are useful for the diagnosis and classification of these disorders.
Translational and clinical research
Participation in phase II-III clinical trials has contributed to the introduction of novel agents including bortezomib and lenalidomide in daily clinical practice. Further participation in such trials for new agents including carfilzomib, elotuzumab en panobinostat is ongoing.