Development of Sophisticated Flow Cytometric Diagnostics for Hematological Disorders

Hematological diseases encompass various disorders affecting blood, bone marrow, and lymphatic systems. They range from anemia to leukemia, impacting blood cell production, function, or structure, and leads to various symptoms such as fatigue, night sweats, thrombosis, anemia, bleedings, and increased susceptibility to infections.

The purpose of this proposal is to develop better diagnostic tools for clonal hematological diseases with a specific focus on myelodysplastic syndrome (MDS) and high-grade lymphomas.  

To do this we will; a) assess cell surface markers, intracellular molecules, and DNA content simultaneously by flow cytometry, and b) link these phenoptypic data to morphological, molecular, and cytogenetic information and ultimately to patient outcome. We aim at enhancing the analysis quality and objectivity to facilitate targeted, and personalized treatment strategies that ultimately will improve patient outcomes and quality of life.  

 If successful this proposal will improve the diagnostic tools for diseases like acute leukemias, lymphomas, MDS and myeloproliferative neoplasms (MPN). Our objective is to develop novel flow cytometric methods to assess the cause of anemia and the aggressiveness of different lymphomas, which can be promptly applied in a clinical setting and provide more accurate and detailed patient specific information to the clinician. Parts of the project is run in close collaboration with two patient representatives from the Blood cancer foundation (Blodcancerförbundet)

Focus on immunoregulatory cells in advanced immunological therapies.

During the last decades, new immunotherapeutics have evolved, including a wide range of monoclonal or bispecific antibodies, immunomodulatory small molecules, and CAR-T cells. These have dramatically improved the outcome for several types of cancer and autoimmune diseases. Yet, not all patients respond, and there are probably several reasons for that but a counteracting role of  regulatory cells like myeloid-derived suppressor cells (MDSCs)and granulocytes have been suggested as important players.

The aim of this project is to map quantitative, functional and gene expression changes in immunoregulatory cells in patients with mature B-cell malignancies or with autoimmune diseases. By studying immunoregulatory cells in two completely diverse disease settings such as mature B-cell malignancy and autoantibody driven autoimmunity we seek to broaden our perspectives and gain new insights into immune regulation. The focus of our investigations will be on the regulatory functions of granulocytes and MDSCs, and their effects on plasma cells, regulatory T cells (Tregs) and T follicular helper cells (Tfh).

If achieved, the project will enhance our understanding of immunoregulatory cells in cancer and autoimmunity. In the long term, this will result in: (a) the development of treatments tailored to the immune system's status, and (b) the ability to modify the immunoregulatory cells of individual patients to either suppress inflammation in autoimmune conditions or boost the immune response in cancer.