Myelodysplastic syndromes (MDS) are predominately ageing-related haematopoietic disorders that are notorious for their heterogeneity and ineffective haematopoiesis, which is reflected by a hypercellular, dysplastic bone marrow next to cytopenias. The heterogeneity included by MDS extends from the pathophysiology to the clinical phenotypes. Although MDS are defined as hematopoietic stem cell (HSC) disorders, perturbations of the bone marrow and immune microenvironment are known to contribute to their pathogenesis. The clinical course of MDS ranges from a stable disease with a near-normal life expectancy and unrelated death to transformation towards acute myeloid leukaemia (AML) or progressive bone marrow failure. This heterogeneity can be problematic for clinicians, who rely on clinical models for estimating prognosis and guiding therapeutic decisions. In Chapter 1 we explained the purpose of these clinical models. Classification models use clinical, morphological and cytogenetic data to stratify MDS patients into homogeneous groups with intrinsic diagnostic and prognostic information. Prognostic scoring systems intend to estimate the probability of survival and disease progression to guide therapy decision-making. The aim of this thesis was twofold. The first objective was to investigate current methods to handle MDS heterogeneity, i.e. by clinical classification models and prognostic scoring systems (Part I). The second objective was to identify biomarkers that contribute to the dissection of MDS based of the study of the hematopoietic stem and progenitor cells, glycan profiles and the immune microenvironment (Part II).
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