Project Details
B-Cell Precursor Lymphoma as a model for immune control, dissemination and low-risk subgroups of precursor cell neoplasms
Applicant
Professor Dr. Wolfram Klapper
Subject Area
Hematology, Oncology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 444949889
Precursor B-cell (PBC) neoplasms are diseases that have properties of immature B-cells. Because the malignant cells can usually be found in the blood and bone marrow, the diseases are also known as PBC leukemia. In some patients, however, the malignant cells are occur within the tissues (e.g. lymph nodes) and are absent from the blood and bone marrow. These diseases are known as PBC lymphomas. Since the presentation of the disease as lymphoma is much rarer than the presentation as leukemia, the PBC lymphomas have almost not been studied molecularly yet. However, clinical observations indicate that the PBC lymphoma may have properties distinct from leukemia. Particularly limited stages of the lymphoma disease can be cured with less chemotherapy than is the case for leukemia. In the Hematopathology Section in Kiel, we have been able to gather a worldwide unique collection of PBC lymphomas over the past decades. This was possible because we serve as the central diagnostics unit for the study group that cares for children with PBC lymphomas (NHL-BFM study group). As a result, we are one of the only centers in the world able to carry out meaningful analyzes of the disease. Research on PBC lymphomas has to apply methods differing in part from leukemia, because the tissue specimen with malignant cells is small and embedded in wax (paraffin). We have therefore developed a portfolio of methods suitable for this type of bio-material, successfully applied it to other B-cell lymphomas in children and thus recognized the differences between the diseases in childhood and adulthood. In the project applied for, we plan to use our unique tissue collection from PBC lymphomas to understand the molecular properties of PBC lymphomas. In preliminary experiments we tested for the most common chromosomal changes (translocations) known to occur in PBC leukemias. Interestingly, the frequency of these translocations is different in lymphoma compared to leukemia. These first result raise hope that with the intended much more precise molecular analysis of the lymphomas and the comparison with leukemia, we will understand why the diseases present themselves so differently. We expect to find evidence of how the immune system is preventing the neoplastic cells in lymphoma from disseminating in the blood and presenting them as leukemia. Within the collaborative research group, we can interrelate or results on lymphomas with findings in leukemia. The attempt to find a “molecular counterpart” of the PCB lymphomas among the PCB leukemias is linked to the hope of being able to treat some leukemias with less chemotherapy.
DFG Programme
Clinical Research Units