Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), and acute leukemias (ALs) are clonal hematological disorders resulting from multiple genetic alterations in hematological stem cells.

MDS is characterized by profound cytopenias due to ineffective hematopoiesis resulting in a significant decline in quality and quantity of life. Life expectancy in a newly diagnosed MDS patient varies from a couple of months to ten years. MPNs are a group of related hematological disorders characterized by the excessive formation of mature blood cells. Both MPN and MDS have a tendency to transform into acute myeloid leukemia (AML), which significantly worsens the prognosis of the disease. Most commonly, these diseases are diagnosed in patients over 50 years of age and familial predisposition should be suspected in patients acquiring the disease in early adulthood or in childhood.

ALs, in turn, consist of a group of hematopoietic neoplasms involving patients of all ages. Cancer cells, namely blasts, reside in the patient’s bone marrow and are characterized by an impaired capacity to develop into mature myeloid or lymphoid blood cells. Depending on the age and performance status of the patient and subtype of the disease, acute leukemias lead to death in 10-80% of cases despite the given anti-cancer therapy. Ascertaining pathological events occurring in hematopoiesis also uncovers the path to understanding normal physiological processes in blood cell development.

Already today, the detection of germline mutations also affects the mode of therapy e.g. timing of stem cell transplantation and selection of the donor. Knowledge of the prevalence of mutations, their penetrance and effects on the clinical phenotype is also a prerequisite for successful genetic counseling. In addition to dominant high-penetrance mutations, relatively common genetic variations may contribute to tumorigenesis.

The aim of our research is to understand how inherited and acquired genetic factors contribute to the development and clinical course of hematological malignancies.