Midway evaluation - Kristoffer Sand
The immune system in Myelodysplastic syndromes
Myelodysplastic syndromes(MDS) are a group of clonal bone marrow disorders, with dysplastic myeloid progenitor cells, cytopenias and increased risk of transformation to Acute Myeloid Leukemia(AML). The immune system is deregulated in MDS, with increased inflammation in low-risk and a suppressive environment in high-risk MDS.
The aim of the project is to investigate the presence and function of cytotoxic and regulatory components of the immune system in MDS patients, with a main focus on lymphocytes. The main methods for the project are multicolor flow cytometry to investigate cells from fresh and frozen blood and bone marrow samples, and ELISA/Luminex to investigate small molecular mediators (cytokines and chemokines) in serum/plasma and in cell culture media.
We have in article I shown that lymphocytes in peripheral blood samples from MDS patients show a chemokine receptor profile in line with a dominance of cells with a mature phenotype compared to healthy controls. In article II we focus on the presence of the chemokine receptor CX3CR1 in the bone marrow of MDS patients. This receptor is normally associated with a high cytotoxic potential. In article III we have investigated the presence and function of Myloid derived supressor cells (MDSC's) in Myelodysplastic syndromes. In article IV we plan on investigating the levels of cytokines and chemokines in serum of MDS patients, and screen for mediators associated with an increased risk of leukemic transformation.